19590 Federal Register / Vol. 72, No. 74 / Wednesday, April 18, 2007 / Proposed Rules 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 174 

[EPA–HQ–OPP–2006–0642; FRL–8100–7] 

RIN 2070–AD49 

Exemption Under the Federal 

Insecticide, Fungicide, and 

Rodenticide Act for Certain PlantIncorporated Protectants Derived From 

Plant Viral Coat Protein Gene(s) 

(PVCP-PIPs); Supplemental Proposal 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: EPA is proposing to exempt 

from Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) requirements 

plant-incorporated protectants derived 

from plant viral coat protein genes 

(PVCP-PIPs) when the PVCP-PIP meets 

specified criteria. EPA is proposing this 

exemption because the Agency believes 

that the PVCP-PIPs covered by this 

exemption would be of a character 

which is unnecessary to be subject to 

FIFRA in order to carry out the purposes 

of the Act. 

DATES: Comments must be received on 

or before July 17, 2007. 

ADDRESSES: Submit your comments, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2006–0642, by 

one of the following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov/. Follow the online instructions for submitting 

comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S-4400, One 

Potomac Yard (South Building), 2777 S. 

Crystal Drive, Arlington, VA. Deliveries 

are only accepted during the Docket’s 

normal hours of operation (8:30 a.m. to 

4 p.m., Monday through Friday, 

excluding legal holidays). Special 

arrangements should be made for 

deliveries of boxed information. The 

Docket telephone number is (703) 305– 

5805. 

Instructions: Direct your comments to 

docket ID number EPA–HQ–OPP–2006– 

0642. EPA’s policy is that all comments 

received will be included in the docket 

without change and may be made 

available on-line at http:// 

www.regulations.gov, including any 

personal information provided, unless 

the comment includes information 

claimed to be Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

Do not submit information that you 

consider to be CBI or otherwise 

protected through regulations.gov or email. The Federal regulations.gov 

website is an ‘‘anonymous access’’ 

system, which means EPA will not 

know your identity or contact 

information unless you provide it in the 

body of your comment. If you send an 

e-mail comment directly to EPA without 

going through regulations.gov, your email address will be automatically 

captured and included as part of the 

comment that is placed in the docket 

and made available on the Internet. If 

you submit an electronic comment, EPA 

recommends that you include your 

name and other contact information in 

the body of your comment and with any 

disk or CD-ROM you submit. If EPA 

cannot read your comment due to 

technical difficulties and cannot contact 

you for clarification, EPA may not be 

able to consider your comment. 

Electronic files should avoid the use of 

special characters, any form of 

encryption, and be free of any defects or 

viruses. 

Docket: All documents in the docket 

are listed in the docket index. Although 

listed in the index, some information is 

not publicly available, e.g., CBI or other 

information whose disclosure is 

restricted by statute. Certain other 

material, such as copyrighted material, 

is not placed on the Internet and will be 

publicly available only in hard copy 

form. Publicly available docket 

materials are available either in the 

electronic docket at http:// 

www.regulations.gov, or, if only 

available in hard copy, at the OPP 

Regulatory Public Docket in Rm. S-4400, 

One Potomac Yard (South Building), 

2777 S. Crystal Drive, Arlington, VA. 

The hours of operation of this Docket 

Facility are from 8:30 a.m. to 4 p.m., 

Monday through Friday, excluding legal 

holidays. The Docket telephone number 

is (703) 305–5805. 

FOR FURTHER INFORMATION CONTACT: 

Melissa Kramer, Hazard Assessment 

Coordination and Policy Division 

(7202M), Office of Science Coordination 

and Policy, 1200 Pennsylvania Ave. 

NW, Washington, DC 20460–0001; 

telephone number: (202) 564–8497; fax 

number: (202) 564–8502; e-mail address: 

kramer.melissa@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does This Notice Apply to Me? 

You may be potentially affected by 

this action if you are a person or 

company involved with agricultural 

biotechnology that may develop and 

market plant-incorporated protectants. 

Potentially affected entities may 

include, but are not limited to: 

• Pesticide and Other Agricultural 

Chemical Manufacturing (NAICS code 

32532), e.g., establishments primarily 

engaged in the formulation and 

preparation of agricultural and 

household pest control chemicals; 

• Crop Production (NAICS code 111), 

e.g., establishments primarily engaged 

in growing crops, plants, vines, or trees 

and their seeds; 

• Colleges, Universities, and 

Professional Schools (NAICS code 

611310), e.g., establishments of higher 

learning which are engaged in 

development and marketing of virusresistant plants; 

• Research and Development in the 

Physical, Engineering, and Life Sciences 

(NAICS code 54171), e.g., establishment 

primarily engaged in conducting 

research in the physical, engineering, or 

life sciences, such as agriculture and 

biotechnology. 

This listing is not intended to be 

exhaustive, but rather provides a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. To determine whether 

you or your business may be affected by 

this action, you should carefully 

examine the applicability provisions in 

40 CFR part 174. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

B. What Should I Consider as I Prepare 

My Comments for EPA? 

1. Docket. EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ– 

OPP–2006–0642. Publicly available 

docket materials are available either in 

the electronic docket at http:// 

www.regulations.gov, or, if only 

available in hard copy, at the Office of 

Pesticide Programs (OPP) Regulatory 

Public Docket in Rm. S-4400, One 

Potomac Yard (South Building), 2777 S. 

Crystal Drive Arlington, VA. The hours 

of operation of this Docket Facility are 

from 8:30 a.m. to 4 p.m., Monday 

through Friday, excluding legal 

holidays. The Docket telephone number 

is (703) 305–5805. 


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2. Tips for preparing your comments. 

When submitting comments, remember 

to: 

i. Identify the document by docket ID 

number and other identifying 

information (subject heading, Federal 

Register date, and page number). 

ii. Follow directions. The Agency may 

ask you to respond to specific questions 

or organize comments by referencing a 

Code of Federal Regulations (CFR) part 

or section number. 

iii. Explain why you agree or disagree; 

suggest alternatives and substitute 

language for your requested changes. 

iv. Describe any assumptions and 

provide any technical information and/ 

or data that you used. 

v. If you estimate potential costs or 

burdens, explain how you arrived at 

your estimate in sufficient detail to 

allow for it to be reproduced. 

vi. Provide specific examples to 

illustrate your concerns and suggest 

alternatives. 

vii. Explain your views as clearly as 

possible, avoiding the use of profanity 

or personal threats. 

viii. Make sure to submit your 

comments by the comment period 

deadline identified. 

II. Background 

A. What Action is the Agency 

Proposing? 

EPA is proposing an exemption from 

FIFRA for certain plant virus coat 

protein plant-incorporated protectants 

or ‘‘PVCP-PIPs.’’ EPA is proposing to 

define a PVCP-PIP as ‘‘a plantincorporated protectant derived from 

one or more genes that encode a coat 

protein of a virus that naturally infects 

plants. This includes plant-incorporated 

protectants derived from one or more 

plant viral coat protein genes that 

produce only RNA and no virus-related 

protein.’’ PVCP-PIPs introduced into 

plants with the intention of preventing 

or mitigating viral disease meet the 

FIFRA section 2(u) definition of 

‘‘pesticide’’ because they are introduced 

into plants with the intention of 

‘‘preventing, destroying, repelling, or 

mitigating any pest...’’ (7 U.S.C. 136(u)) 

and plant viruses meet the FIFRA 

section 2 definition of ‘‘pest’’ (7 U.S.C. 

136(t)). EPA is proposing this exemption 

because the Agency believes that the 

PVCP-PIPs covered by this exemption 

would be of a character which is 

unnecessary to be subject to FIFRA in 

order to carry out the purposes of the 

Act. 

A PIP can be exempt from the 

requirements of FIFRA, other than the 

adverse effects reporting requirements 

of 40 CFR 174.71, if it meets all three 

of the requirements listed in 40 CFR 

174.21. Section 174.21(a) requires that 

the PIP meet the criteria listed in at least 

one of the sections in §§ 174.25 through 

174.50. Section 174.21(b) requires that 

when the PIP is intended to be 

produced and used in a crop used as 

food, the residues of the PIP are either 

exempted from the requirement of a 

tolerance under FFDCA or no tolerance 

would otherwise be required for the PIP. 

Section 174.21(c) requires that an 

exempt PIP must contain only those 

inert ingredient(s) included on the list 

codified at §§ 174.485 through 174.490. 

(Reference to §§ 174.485 through 

174.490 in § 174.21(c) is proposed to be 

changed to refer to §§ 174.485 through 

174.486 in today’s Proposed Rule.) See 

Unit II.F. for further discussion of these 

§ 174.21 criteria. 

The rule proposed in today’s Federal 

Register would establish 40 CFR 174.27, 

which would contain three criteria that, 

when met, would allow PVCP-PIPs to 

meet the general requirement for 

exemption for all PIPs listed at 40 CFR 

174.21(a). Today’s Federal Register also 

proposes to add several substances 

known to be used as inert ingredients in 

PIPs to 40 CFR part 174 subpart X, 

thereby potentially expanding the 

PVCP-PIPs that could meet the 

conditions of § 174.21(c). A companion 

document published elsewhere in 

today’s Federal Register also proposes a 

tolerance exemption for certain PVCPPIP residues, thereby potentially 

expanding the PVCP-PIPs that could 

meet the conditions of § 174.21(b). 

The three criteria that EPA is 

proposing to insert at 40 CFR 174.27 are 

intended to address three issues that 

may be associated with a PVCP-PIP. 

These issues are: 

• The potential for increased 

weediness or invasiveness of the crop 

plant containing the PVCP-PIP or any 

wild or weedy relatives that could 

acquire the PVCP-PIP through gene flow 

thereby causing negative effects on 

either the agro-ecosystem or natural 

environments. This issue is addressed 

in proposed § 174.27(a). 

• The potential that viruses with 

novel properties could develop through 

novel viral interactions. This issue is 

addressed in proposed § 174.27(b). 

• The potential for human or 

nontarget organism exposure to proteins 

that have not previously existed in 

nature and thus should be examined to 

determine whether they have 

potentially toxic or allergenic 

properties. This issue is addressed in 

proposed § 174.27(c). 

In order to satisfy 40 CFR 174.21(a), 

a PVCP-PIP would have to satisfy 

proposed § 174.27(a), (b), and (c). The 

requirements at § 174.27(d) would also 

have to be met to qualify for exemption. 

Proposed § 174.27(a), (b), and (c) each 

can be met in one of two ways: a 

product developer may self-determine 

that paragraph (1) of the criterion 

applies (i.e., § 174.27(a)(1), (b)(1), or 

(c)(1)) or the Agency may determine that 

paragraph (2) of the criterion applies 

(i.e., § 174.27(a)(2), (b)(2), or (c)(2), 

respectively). Paragraph (1) of each 

proposed criterion (i.e., § 174.27(a)(1), 

(b)(1), and (c)(1)) describes an objective, 

well-defined characteristic. Therefore, 

the developer may determine whether 

the PVCP-PIP meets the requirement. 

Paragraph (2) of each proposed criterion 

(i.e., § 174.27(a)(2), (b)(2), and (c)(2)) is 

conditioned on an Agency 

determination because it may involve 

analysis of several types of information. 

Each criterion may be satisfied either by 

self determination under paragraph (1) 

or Agency determination under 

paragraph (2) irrespective of how the 

other two criteria are satisfied; there is 

no requirement that all three criteria 

must be satisfied under either paragraph 

(1) or paragraph (2) in order to qualify 

for the exemption. 

B. What is the Agency’s Authority for 

Taking this Action? 

This rule is promulgated under the 

authority of FIFRA sections 3(a), 25(a), 

and 25(b) (7 U.S.C. 136a(a), 136w(a), 

and 136w(b)). 

FIFRA section 3(a) states that, except 

as provided by the Act, no person may 

distribute or sell in the United States 

any pesticide that is not registered 

under the Act (7 U.S.C. 136(a)). FIFRA 

section 2(u) defines ‘‘pesticide’’ as: ‘‘(1) 

any substance or mixture of substances 

intended for preventing, destroying, 

repelling, or mitigating any pest, (2) any 

substance or mixture of substances 

intended for use as a plant regulator, 

defoliant, or desiccant, and (3) any 

nitrogen stabilizer...’’ (7 U.S.C. 136(u)). 

Under FIFRA section 2(t), the term 

‘‘pest’’ includes ‘‘(1) any insect, rodent, 

nematode, fungus, weed, or (2) any 

other form of terrestrial or aquatic plant 

or animal life or virus, bacteria, or other 

microorganism... which the 

Administrator declares to be a pest...’’

subject to certain exceptions (7 U.S.C. 

136(t)). 

Before EPA may register a pesticide 

under FIFRA, the applicant must show 

that the pesticide ‘‘when used in 

accordance with widespread and 

commonly recognized practice... will 

not generally cause unreasonable 

adversese effects on the environment’’

(7 U.S.C. 136a(c)(5)(D)). The term 

‘‘environment’’ includes ‘‘water, air, 

land, and all plants and man and other 


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animals living therein, and the 

interrelationships which exist among 

these’’ (7 U.S.C. 136(j)). FIFRA section 

2(bb) defines the term ‘‘unreasonable 

adverse effects on the environment’’ to 

mean: ‘‘(1) any unreasonable risk to man 

or the environment, taking into account 

the economic, social, and environmental 

costs and benefits of the use of any 

pesticide, or (2) a human dietary risk 

from residues that result from a use of 

a pesticide in or on any food 

inconsistent with the standard under 

section 408 of the Federal Food, Drug, 

and Cosmetic Act’’ (7 U.S.C. 136(bb)). 

Although FIFRA requires the 

registration of most pesticides, it also 

authorizes the regulation of unregistered 

pesticides. FIFRA section 3(a) provides 

that, to the extent necessary to prevent 

unreasonable adverse effects on the 

environment, the Administrator may 

limit the distribution, sale, or use of any 

pesticide that is not registered under 

section 3 of FIFRA, subject to an 

experimental use permit under section 5 

of FIFRA, or subject to an emergency 

exemption under section 18 of FIFRA. 

Pesticides that are ‘‘not registered’’

include pesticides that are exempt from 

FIFRA requirements under section 

25(b). 

An unregistered pesticide may be 

distributed or sold if it is exempted by 

regulation under FIFRA section 25(b). 

Under FIFRA section 25(b)(2), the 

Agency can exempt pesticides from 

some or all of the requirements of 

FIFRA when the Agency determines 

that the pesticide is ‘‘of a character 

which is unnecessary to be subject to 

[FIFRA] in order to carry out the 

purposes of this Act’’ (7 U.S.C. 

136w(b)(2)). EPA interprets section 

25(b)(2) to authorize the Agency to 

exempt a pesticide or category of 

pesticides that EPA determines (1) poses 

a low probability of risk to the 

environment and (2) is not likely to 

cause unreasonable adverse effects to 

the environment even in the absence of 

regulatory oversight under FIFRA. This 

standard differs from the standard for 

registration which considers only 

whether the pesticide ‘‘when used in 

accordance with widespread and 

commonly recognized practice... will 

not generally cause unreasonable 

adverse effects on the environment’’ (7 

U.S.C. 136a(c)(5)(D)). 

In evaluating the first condition that 

must be met for the Agency to exempt 

a pesticide, i.e., whether use of the 

pesticide poses a low probability of risk 

to the environment, EPA considers the 

extent of the potential risks caused by 

use of the pesticide to the environment, 

including humans and other animals, 

plants, water, air and land. Potential 

risks to humans include dietary risks as 

well as non-dietary risks such as those 

resulting from occupational or 

residential exposure to the pesticide. 

EPA uses the FFDCA section 408 

standard in evaluating dietary risks as 

discussed in Unit II.C. of this preamble. 

EPA will not exempt pesticides unless 

they pose a low probability of risk to the 

environment. 

In evaluating the second condition 

that must be met for the Agency to 

exempt a pesticide, i.e., whether the use 

of the pesticide is unlikely to cause 

unreasonable adverse effects on the 

environment even in the absence of 

regulatory oversight under FIFRA, EPA 

balances all the potential risks to human 

health, including dietary risks (see Unit 

II.C. of this preamble for discussion of 

the FFDCA standard), and risks to the 

remainder of the environment from use 

of the pesticide against the potential 

benefits associated with its use. In 

balancing risks and benefits, EPA 

considers the economic, social, and 

environmental costs and benefits of the 

use of the pesticide. If the pesticide 

poses a low probability of risk to the 

environment and is not likely to cause 

unreasonable adverse effects to the 

environment even in the absence of 

regulatory oversight under FIFRA, EPA 

may exempt the pesticide from 

regulation under FIFRA. 

C. What is the Relationship of FIFRA 

Exemptions to the FFDCA Section 408 

Standard? 

Under FFDCA section 408(a), a 

pesticide chemical residue in or on a 

food (hereafter simply ‘‘in food’’) is not 

considered safe unless EPA has issued 

a tolerance for the residue and the 

residue is within the established 

tolerance limit or EPA has issued an 

exemption from the requirement of a 

tolerance for the residue (21 U.S.C. 

346a(a)(1)). FFDCA section 408 

authorizes EPA to determine a residue 

is safe and therefore exempt from the 

requirement of a tolerance if the 

Administrator ‘‘has determined that 

there is a reasonable certainty that no 

harm will result from aggregate 

exposure to the pesticide chemical 

residue, including all anticipated 

dietary exposures and all other 

exposures for which there is reliable 

information’’ (21 U.S.C. 

346a(c)(2)(A)(ii)). Section 408 of the 

FFDCA also directs EPA to specifically 

consider harm that may result to infants 

and children as a result of pesticide 

chemical residues. For additional 

discussion of this standard, see the 

Exemption from the Requirement of a 

Tolerance under the Federal Food, Drug, 

and Cosmetic Act for Residues of Plant 

Virus Coat Proteins that are Part of a 

Plant-Incorporated Protectant published 

concurrently in today’s Federal 

Register. 

EPA uses the FFDCA section 408 

safety standard in evaluating whether a 

pesticide used in food meets the FIFRA 

section 25(b)(2) exemption standard 

with respect to human dietary risk. A 

pesticide in food poses a low probability 

of human dietary risk if it meets the 

FFDCA section 408 standard for an 

exemption from the requirement of a 

tolerance. Such a pesticide also is not 

likely to cause unreasonable adverse 

effects to the environment, with respect 

to human dietary risk only, if the dietary 

risks resulting from use of that pesticide 

are consistent with the FFDCA section 

408 exemption standard, and the 

potential benefits of use outweigh any 

dietary risk even in the absence of 

regulatory oversight. 

FIFRA, however, does not provide for 

exemption of a pesticide in food based 

solely upon human dietary risk and 

consistency with the FFDCA section 408 

exemption standard; an exemption from 

the requirements of FFDCA does not 

exempt a product from regulation under 

FIFRA. For an exemption under FIFRA, 

EPA must also evaluate non-dietary 

risks to humans and the remainder of 

the environment from the pesticide and 

determine both that the pesticide poses 

only a low probability of non-dietary 

risks and that use of the pesticide is not 

likely to cause any unreasonable 

adverse effects to the environment from 

such nondietary risks in the absence of 

regulation. 

D. What is the Role of Other Federal 

Agencies? 

EPA is the Federal agency responsible 

for the regulation of pesticides. Under 

the Coordinated Framework for 

Regulation of Biotechnology (51 FR 

23302, June 26, 1986), EPA works 

closely with the U.S. Department of 

Agriculture (USDA), which has 

responsibilities under the Plant 

Protection Act (PPA), and the U.S. Food 

and Drug Administration (FDA), which 

has responsibilities under FFDCA. EPA, 

USDA, and FDA consult and exchange 

information when such consultation is 

helpful in resolving safety questions. 

The three agencies also strive for 

consistency between programs 

following one of the basic tenets of the 

Coordinated Framework, i.e., that the 

agencies composing the Framework 

adopt consistent approaches to the 

extent permitted by the respective 

statutory authorities. A consistent 

approach between agencies is easier for 

the regulated community to understand, 

and it likely conserves resources 


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because data developed for one agency 

may meet at least some of the 

requirements posed by another agency 

for the same or similar products. 

1. USDA. USDA has the responsibility 

of preventing the introduction and 

dissemination of plant pests under the 

PPA. Before a genetically engineered 

plant that is subject to the PPA may be 

introduced into the environment, 

approval must be obtained from the 

USDA/Animal Plant Health Inspection 

Service (APHIS) unless such a plant has 

been reviewed and granted 

Nonregulated Status. The USDA 

regulations use genetic engineering and 

potential plant pest risk as criteria for 

determining the scope of its regulations 

(62 FR 23945, May 2, 1997). Any 

genetically engineered plant that 

contains genetic material from a plant 

pest is subject to the regulations. Thus, 

all plants containing PVCP-PIPs are 

subject to USDA/APHIS requirements 

under the PPA. 

EPA therefore recognizes that there is 

a potential for duplicative oversight 

with respect to certain issues that may 

arise in decisions about PVCP-PIPs that 

require any review by EPA. For 

example, in its reviews of Petitions for 

Determination of Nonregulated Status 

under regulations at 7 CFR part 340, the 

potential for weediness, for 

displacement of native species, and 

potential consequences of gene transfer 

are evaluated by USDA/APHIS. EPA 

and USDA/APHIS will continue to 

consult and collaborate on reviews of 

PVCP-PIPs. EPA and USDA/APHIS will 

work together to avoid potential 

duplication and inconsistencies and to 

coordinate their analyses in accordance 

with their respective expertise and 

jurisdiction. 

2. FDA. FDA is the primary U.S. 

agency responsible for ensuring the 

safety of commercial food and food 

additives. FDA’s authority under 

FFDCA extends to any nonpesticidal 

substance that may be introduced into a 

new plant variety and that is expected 

to become a component of food. 

Pursuant to sections 201 and 408 of 

FFDCA and the creation of EPA, 

pesticide chemical residues are subject 

to EPA’s regulatory authority under 

FFDCA. 

E. What is a PVCP-PIP? 

EPA is proposing to define a PVCPPIP as ‘‘a plant-incorporated protectant 

derived from one or more genes that 

encode a coat protein of a virus that 

naturally infects plants. This includes 

plant-incorporated protectants derived 

from one or more plant viral coat 

protein genes that produce only RNA 

and no virus-related protein.’’

Coat proteins are those substances 

that viruses produce to encapsulate and 

protect the viral nucleic acid and to 

perform other important tasks for the 

virus, e.g., assistance in viral 

replication, movement within the plant, 

and transmission of the virus from plant 

to plant by insects (Ref. 1). In many 

cases, when the genetic material 

encoding a plant virus coat protein is 

engineered into a plant’s genome, the 

plant displays resistance to infection by 

that virus as well as other viruses 

having similar coat protein sequences 

(Ref. 2). 

Current scientific information 

suggests that prevention or mitigation of 

disease by PVCP-PIPs may occur by two 

different mechanisms. For some PVCPPIPs, resistance is believed to be 

protein-mediated because efficacy is 

correlated with the concentration of coat 

protein produced by the transgene (Ref. 

3). In protein-mediated resistance, the 

coat protein is thought to impede the 

infection cycle by interfering with the 

disassembly of infecting viruses (Ref. 4). 

In transgenic plants, a second 

mechanism of resistance, posttranscriptional gene silencing (PTGS) 

may be activated. In PTGS, prevention 

or mitigation of viral disease is not 

correlated with the level of coat protein 

expression. Indeed, virus resistance can 

occur even when a coat protein gene 

expresses untranslatable RNA sequences 

and no coat protein is detected (Ref. 4). 

PTGS is a defense mechanism in plants 

against foreign RNA (e.g., viruses) in 

which sequence-specific RNA 

degradation is initiated by the plant in 

response to the foreign RNA itself. 

Evidence suggests that PTGS is initiated 

once there is a threshold accumulation 

of double-stranded (ds) RNA in the cell 

cytoplasm (Ref. 5). Over 90% of plant 

viruses have single-stranded RNA 

genomes, but viral replication 

transiently produces dsRNA in 

quantities sufficient to trigger PTGS 

(Ref. 6). PTGS is also known to occur 

with transgenes that are transcribed at a 

low level but that likely produce dsRNA 

(Ref. 7). Once the plant recognizes the 

dsRNA, it is thought to be cleaved by a 

dsRNA-specific nuclease to produce 

small 21- to 25-nucleotide short 

interfering RNA sequences (siRNAs; Ref. 

8). The siRNAs are thought to serve as 

guides for the cleavage of singlestranded RNA with a sequence similar 

to the dsRNAs (Ref. 9). Thus once PTGS 

is initiated, it targets all RNA with high 

sequence similarity to the sequence that 

initiated the process, regardless of 

whether it was transcribed from the 

transgene, an endogenous gene, or viral 

RNA. 

A plant virus coat protein transgene 

that confers virus resistance through 

either a protein- or RNA-mediated 

mechanism would fall within EPA’s 

proposed definition of a PVCP-PIP. The 

substances involved in either 

mechanism of resistance would meet 

the FIFRA definition of a pesticide 

because the transgene and any material 

expressed from the transgene are 

introduced into a plant for the purpose 

of preventing or mitigating viral disease 

(see Unit II.A.). 

The proposed definition of a PVCPPIP contains the phrase ‘‘naturally 

infects plants.’’ Including this phrase in 

the definition would specifically limit 

the proposed exemption by requiring 

that the virus coat protein gene 

sequence used in the PVCP-PIP be based 

exclusively on a plant virus sequence. 

This limitation is proposed in order to 

exclude from the definition any coat 

proteins of plant viruses that have been 

modified with sequences from animal or 

human viruses. EPA includes this 

concept in today’s proposal in response 

to comment received from the public in 

earlier Federal Register documents 

pertaining to PVCP-PIPs. 

F. What Conditions Must be Met for a 

PVCP-PIP to Qualify for a FIFRA 

Exemption? 

As noted above, a PIP is exempt from 

the requirements of FIFRA, other than 

the adverse effects reporting 

requirements of 40 CFR 174.71, if the 

PIP meets the requirements in 40 CFR 

174.21(a), (b), and (c). Therefore, the 

following factors need to be considered 

to determine the FIFRA status of a 

PVCP-PIP. First, does the PVCP-PIP 

meet the requirement at 40 CFR 

174.21(a)? Second, do the residues of 

the PVCP-PIP meet the requirement at 

40 CFR 174.21(b)? Third, do the inert 

ingredients that are part of the PVCP-PIP 

meet the requirement at 40 CFR 

174.21(c)? 

1. Does the PVCP-PIP meet the 

requirement at 40 CFR 174.21(a)? 

Section 174.21(a) requires that the PIP 

meet the criteria listed in at least one of 

the sections in §§ 174.25 through 

174.50. Today’s action proposes to 

establish § 174.27, which would contain 

criteria allowing certain PVCP-PIPs to 

meet the § 174.21(a) requirement for 

exemption. These criteria identify those 

PVCP-PIPs that EPA has been able to 

determine meet the standard under 

FIFRA section 25(b)(2), i.e., that pose a 

low probability of risk to the 

environment and that are not likely to 

cause unreasonable adverse effects to 

the environment even in the absence of 

regulatory oversight under FIFRA. EPA 

is proposing criteria that address the 


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relevant potential risks associated with 

these products: 

i. The potential for increased 

weediness or invasiveness of the crop 

plant containing the PVCP-PIP or any 

wild or weedy relatives that could 

acquire the PVCP-PIP through gene flow 

thereby causing negative effects on 

either the agro-ecosystem or natural 

environments. This issue is addressed at 

§ 174.27(a) and is referred to as 

‘‘weediness’’ for the purposes of this 

document. 

ii. The potential for viruses with 

novel properties developing through 

novel viral interactions. This issue is 

addressed at § 174.27(b) and is referred 

to as ‘‘viral interactions’’ for the 

purposes of this document. 

iii. The potential for human or 

nontarget organism exposure to proteins 

that may not have previously existed in 

nature and thus should be examined to 

determine whether they have 

potentially toxic or allergenic 

properties. This issue is addressed at 

§ 174.27(c) and is referred to as ‘‘protein 

production’’ for the purposes of this 

document. 

Proposed §§ 174.27(a), (b), and (c) are 

discussed in greater detail in Unit III of 

this Federal Register document. In 

addition, a graphical depiction of what 

this rule is proposing is available in the 

docket for this proposed rule. 

2. Do the residues of the PVCP-PIP 

meet the requirement at 40 CFR 

174.21(b)? Section 174.21(b) requires 

that in order to qualify for a FIFRA 

exemption, the residues of a PVCP-PIP 

that is intended to be produced and 

used in a crop used as food must either 

be exempted from the requirement of a 

tolerance under FFDCA or no tolerance 

would otherwise be required for the 

PVCP-PIP. Therefore, if a PVCP-PIP is 

used in a food plant (e.g., the PVCP-PIP 

is produced and used in a corn plant) 

or residues of the PVCP-PIP might 

reasonably be expected in food (e.g., the 

PVCP-PIP is produced and used in an 

ornamental plant but could move 

through gene flow to a sexually 

compatible food plant), the FFDCA 

section 408 requirements must be 

considered when determining whether 

the PVCP-PIP can be exempted under 

FIFRA. If a PVCP-PIP would not be used 

in and would not reasonably be 

expected in a crop used as food (e.g., the 

PVCP-PIP is produced and used in an 

ornamental plant with no sexually 

compatible relatives that are food 

plants), the FFDCA section 408 

requirements do not need to be 

considered. 

EPA anticipates that in most cases the 

PVCP-PIP residues will consist of 

residues of nucleic acids, residues of 

inert ingredients, and residues of the 

plant virus coat protein portion of the 

PVCP-PIP (the ‘‘PVC-protein’’). Residues 

of nucleic acids are exempt from the 

requirement of a tolerance at 40 CFR 

174.475. As of the time this proposed 

rule is being issued, residues of those 

inert ingredients that are exempt from 

the requirement of a tolerance are listed 

at 40 CFR part 180 and 40 CFR part 174 

subpart W. In a companion piece 

appearing in today’s Federal Register, 

EPA is proposing a tolerance exemption 

for residues of certain PVC-proteins that 

meet specified criteria. Due to different 

statutory requirements, the proposed 

FFDCA exemption criteria differ from 

the criteria proposed in this Federal 

Register for 40 CFR 174.27 under 

FIFRA. 

3. Do the inert ingredients that are 

part of the PVCP-PIP meet the 

requirement at 40 CFR 174.21(c)? 

Section 174.21(c) requires that in order 

for a PIP to qualify for exemption any 

inert ingredient contained in the PIP 

must be codified at subpart X of 40 CFR 

part 174 - List of Approved Inert 

Ingredients. Subpart X lists the inert 

ingredients (i) that may be used in a 

plant-incorporated protectant listed in 

subpart B (Exemptions) of part 174 and 

(ii) whose residues are either exempted 

from the requirement of a tolerance 

under FFDCA or no tolerance would 

otherwise be required. EPA is proposing 

to add several substances known to be 

used commonly as inert ingredients in 

PIPs to 40 CFR part 174 subpart X. 

These substances already have tolerance 

exemptions under FFDCA. EPA 

proposes in today’s Federal Register 

that these substances, when used in 

exempt PIPs as inert ingredients under 

specified conditions, should also be 

exempt from FIFRA because they are of 

a character which is unnecessary to be 

subject to FIFRA in order to carry out 

the purposes of the Act. 

G. What if a PVCP-PIP Does Not Qualify 

for Exemption? 

If EPA is unable to conclude that a 

PVCP-PIP meets the standard for 

exemption, an applicant may still apply 

to register the PVCP-PIP under section 

3 of FIFRA. EPA may be able to 

conclude that the PVCP-PIP meets the 

standard for registration (i.e., when it is 

used in accordance with widespread 

and commonly recognized practice, it 

will not generally cause unreasonable 

adverse effects on the environment). 

EPA recognizes that the proposed 

exemption criteria may not identify all 

low risk PVCP-PIPs. A case-by-case 

review for registration would allow the 

Agency to evaluate factors not readily 

incorporated into clear, unambiguous 

exemption criteria. As part of 

registration, the Agency could also 

impose conditions of use as appropriate. 

As is EPA’s general practice regarding 

registration of PIPs, the Agency will 

consult with USDA in evaluating PVCPPIPs for registration. 

H. What is the History of this Proposal? 

1. Scientific input. EPA sponsored or 

cosponsored with other Federal 

agencies, six conferences relevant to 

development of this proposed rule: on 

October 19–21, 1987, a meeting on 

‘‘Regulatory Considerations: Genetically 

Engineered Plants’’ at Cornell 

University in Ithaca, New York; on 

September 8–9, 1988, a ‘‘Transgenic 

Plant Conference’’ in Annapolis, 

Maryland; on November 6–7, 1990, a 

conference on ‘‘Pesticidal Transgenic 

Plants: Product Development, Risk 

Assessment, and Data Needs’’ in 

Annapolis, Maryland; on April 18–19, 

1994, a ‘‘Conference on Scientific Issues 

Related to Potential Allergenicity in 

Transgenic Food Crops’’ in Annapolis, 

Maryland; on July 17–18, 1997, a ‘‘Plant 

Pesticide Workshop’’ in Washington, 

DC; and on December 10–12, 2001 a 

conference on ‘‘Assessment of the 

Allergenic Potential of Genetically 

Modified Foods’’ in Chapel Hill, North 

Carolina. EPA incorporated information 

from these conferences in development 

of this proposed rule as appropriate. 

EPA has requested the advice of two 

scientific advisory bodies at five 

meetings while developing its approach 

to plant-incorporated protectants. On 

December 18, 1992, EPA convened a 

FIFRA Scientific Advisory Panel (SAP) 

to review a draft policy on PIPs (then 

called plant-pesticides) and to respond 

to a series of related questions posed by 

the Agency dealing primarily with 

EPA’s approach under FIFRA. On July 

13, 1993, EPA requested the advice of a 

Subcommittee of the EPA Biotechnology 

Science Advisory Committee (BSAC) on 

a series of scientific questions dealing 

with EPA’s approach to PIPs under 

FFDCA. On January 21, 1994, EPA 

asked for advice on the Agency’s 

approach to PIPs under both statutes at 

a joint meeting of the SAP and the 

BSAC. To evaluate more recent 

scientific advances, EPA again brought 

these issues to a FIFRA SAP meeting on 

October 13–14, 2004. On December 6–

8, 2005, EPA convened a SAP meeting 

to address a series of scientific questions 

related to this proposal. EPA 

incorporated advice from all five 

meetings in development of this 

proposed rule as appropriate. 

2. Federal Register documents. The 

history of this proposal consists of the 

original proposed exemption from 


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FIFRA requirements that appeared in 

the November 23, 1994 Federal Register 

(59 FR 60519); the original proposed 

exemption from FFDCA tolerance 

requirements in the November 23, 1994 

Federal Register (59 FR 60545); and 

several supplemental documents 

appearing in the May 16, 1997 Federal 

Register (59 FR 27149), the July 22, 

1996 Federal Register (61 FR 37891), 

the April 23, 1999 Federal Register (64 

FR 19958), and the July 19, 2001 

Federal Register (66 FR 37772 and 

37855). 

i. November 23, 1994. In a document 

that appeared in the November 23, 1994 

Federal Register (59 FR 60519) (FRL–

4755–3), EPA proposed two alternatives 

under FIFRA section 25(b)(2) to exempt 

PVCP-PIPs from FIFRA requirements. 

Option 1 proposed to categorically 

exempt plant-pesticides derived from 

coat proteins from plant viruses (now 

called PVCP-PIPs). Option 2 proposed a 

more limited exemption covering only 

those PVCP-PIPs that would have the 

least potential to confer selective 

advantage on free-living wild relatives 

of the plants that could acquire the 

PVCP-PIP through gene flow (discussed 

in detail in Unit III.C.3.). 

Elsewhere in the November 23, 1994, 

Federal Register (59 FR 60545) (FRL–

4755–4), EPA proposed to exempt from 

the FFDCA requirement of a tolerance, 

residues of plant virus coat proteins 

produced and used in living plants as a 

plant-incorporated protectant (then 

called a plant-pesticide). The proposed 

exemption from the requirement of a 

tolerance read, ‘‘Residues of coat 

proteins from plant viruses, or segments 

of the coat proteins, produced in living 

plants as plant-pesticides are exempt 

from the requirement of a tolerance’’ (59 

FR 60547). 

ii. May 16, 1997. In August of 1996, 

Congress enacted the Food Quality 

Protection Act (FQPA), which amended 

FFDCA and FIFRA. On May 16, 1997, 

EPA published a supplemental 

document in the Federal Register (62 

FR 27149) (FRL–5716–6) to provide the 

public with an opportunity to comment 

on EPA’s analysis of how certain FQPA 

amendments to FFDCA and FIFRA 

applied to the 1994 proposed exemption 

from the requirement of a tolerance for 

residues of viral coat proteins produced 

in plants as part of a PIP. (Today’s 

Federal Register terms such entities 

‘‘PVC-proteins.’’) 

In the 1997 supplemental document, 

EPA explained how most of the 

substantive factors that the amended 

FFDCA requires EPA to consider in 

evaluating pesticide chemical residues 

had been considered in the Agency’s 

1994 proposed tolerance exemption. 

Even though the Agency may not have 

used the terminology specified in the 

FQPA, EPA did take into account most 

of the factors (e.g., toxicity and 

consumption patterns) in issuing its 

1994 proposal to exempt residues of 

PVC-proteins, or residues of segments of 

such proteins, from FFDCA tolerance 

requirements. EPA therefore sought 

comment on the requirements imposed 

by FQPA that the Agency had not 

addressed in its 1994 proposal, 

specifically: 

a. EPA’s conclusion that there are no 

substances outside of the food supply 

that may have a cumulative toxic effect 

with residues of PVC-proteins, 

b. EPA’s conclusion that there are no 

substances outside of the food supply to 

which humans might be exposed 

through non-occupational routes of 

exposure that are related via a common 

mechanism of toxicity to residues of 

PVC-proteins, 

c. Any available information on PVCproteins causing estrogenic effects, 

d. EPA’s rationale, described in 

greater detail, for concluding that PIPs 

are likely to present a limited exposure 

of pesticidal substances to humans in 

which the predominant route of 

exposure will be dietary, and 

e. EPA’s rationale, described in 

greater detail, for concluding that the 

Agency’s analysis concerning the 

dietary safety of food containing PVCproteins applies to infants and children 

as well as adults. 

Because of the 1996 FQPA, EPA’s 

final determination under FIFRA for 

PVCP-PIPs in food plants could also be 

affected by comments on the companion 

document in today’s Federal Register 

that proposes a tolerance exemption for 

certain PVCP-PIP residues. 

iii. July 22, 1996. On July 22, 1996, 

EPA issued a supplemental document 

(61 FR 37891) (FRL–5387–4) requesting 

comment on one aspect of its November 

23, 1994 Federal Register document: 

how the concept of inert ingredient 

related to plant-incorporated 

protectants. 

iv. April 23, 1999. On April 23, 1999, 

EPA published a supplemental 

document in the Federal Register (64 

FR 19958) (FRL–6077–6) soliciting 

comment on whether to change the 

name of pesticides produced and used 

in living plants. 

v. July 19, 2001. In July of 2001, EPA 

published a package of notices related to 

PIPs in the Federal Register, including 

a supplemental document (66 FR 37855) 

(FRL–6760–4) that provided the public 

with additional opportunity to comment 

on the FIFRA and FFDCA exemptions 

for PIPs that the Agency proposed in 

1994 but had not yet finalized by 2001. 

EPA also requested comment on the 

information, analyses, and conclusions 

pertaining to these PIPs (including 

PVCP-PIPs) contained in the NRC report 

entitled ‘‘Genetically Modified PestProtected Plants: Science and 

Regulation’’ (Ref. 10). The public was 

given an opportunity to comment on a 

proposal to clarify the language of the 

original 1994 proposals EPA was 

considering in response to public 

comment received on the 1994 proposal. 

In addition, the Agency requested 

additional public comment on several 

scientific issues. Also in the July 19, 

2001 Federal Register (66 FR 37772) 

(FRL–6057–7), EPA changed the name 

of these pesticides from ‘‘plantpesticides’’ to ‘‘plant-incorporated 

protectants’’ or ‘‘PIPs.’’

The documents and reports of the 

meetings described above, including 

associated public comments, are 

available in the public dockets 

established for the associated 

rulemakings as described in Unit IX of 

this preamble. 

Today’s proposed rule completely 

supersedes these previous proposals. 

EPA does not intend to respond to 

comments submitted on those 

proposals. Thus, individuals who 

believe that any comments submitted on 

any of the earlier proposals remain 

germane to today’s proposal, should 

submit them (or relevant portions) again 

during this comment period. 

III. Proposed Exemption Criteria under 

§ 174.27 

A. Structure of the Proposed Exemption 

Criteria under § 174.27 

In order to satisfy the general 

requirement for a FIFRA exemption 

listed at 40 CFR 174.21(a), EPA is 

proposing to add three criteria at 40 CFR 

174.27. As discussed in Unit II.F.1., the 

three criteria that EPA is proposing to 

adopt at 40 CFR 174.27 are intended to 

address three issues that are associated 

with potential risks of PVCP-PIPs. 

The PVCP-PIP would have to meet 

proposed §§ 174.27(a), (b), and (c) to 

satisfy 40 CFR 174.21(a). Proposed 

§§ 174.27(a), (b), and (c) each can be met 

in one of two ways: a product developer 

may self-determine that paragraph (1) of 

the criterion is met (i.e., § 174.27(a)(1), 

(b)(1), or (c)(1)) or the Agency may 

determine that paragraph (2) of the 

criterion is met (i.e., § 174.27(a)(2), 

(b)(2), or (c)(2), respectively). Paragraph 

(1) of each proposed criterion (i.e., 

§ 174.27(a)(1), (b)(1), and (c)(1)) 

describes an objective, well-defined 

characteristic. Therefore, the developer 

may determine whether the PVCP-PIP 

meets the requirement. Paragraph (2) of 


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each proposed criterion (i.e., 

§ 174.27(a)(2), (b)(2), and (c)(2)) is 

conditioned on an Agency 

determination because several types of 

information may need to be evaluated 

using a weight-of-evidence approach to 

determine whether the PVCP-PIP meets 

the requirement and is therefore of a 

nature warranting exemption. 

1. Exemption by self-determination. 

Each criterion may be satisfied under 

either paragraph (1) or paragraph (2) 

irrespective of how the other two 

criteria are satisfied; there is no 

requirement that all three criteria must 

be satisfied under either paragraph (1) 

or paragraph (2) in order for a PVCP-PIP 

to qualify for the exemption. However, 

if a PVCP-PIP satisfies all three criteria 

under paragraph (1) by developer self 

determination (i.e., it meets proposed 

§§ 174.27(a)(1), (b)(1), and (c)(1)) and it 

satisfies §§ 174.21(b) and (c), EPA is 

proposing that the developer submit a 

notification to the Agency of that 

determination and certify that the 

PVCP-PIP qualifies for exemption under 

FIFRA, i.e., that the PVCP-PIP meets 

§§ 174.21(a), (b), and (c). In addition, 

EPA is proposing that the developer 

maintain information adequate to 

support the determination. Such records 

must be made available for EPA 

inspection and copying or be otherwise 

submitted to the Agency for review 

upon request for the duration of time 

that the PVCP-PIP is sold or distributed. 

EPA is proposing that these records be 

kept so that EPA could review a 

particular exemption determination if 

needed at a future date. 

EPA is proposing to require that the 

notifications contain: 

i. The name of the crop (including 

genus and species) containing the 

PVCP-PIP. 

ii. The name of the virus from which 

the coat protein gene was derived. 

iii. The name of the virus(es) to which 

resistance is conferred. 

iv. When available, a unique 

identifier. 

EPA is proposing this notification 

requirement because it provides a 

mechanism that allows the Agency to 

keep a record of all PVCP-PIPs that may 

be sold or distributed. EPA expects that 

such a list would be useful to 

developers whose products are moving 

in international trade because it would 

enable EPA to post information on the 

United States Regulatory Agencies 

Unified Biotechnology Website (found 

at http://usbiotechreg.nbii.gov/database

_pub.asp) indicating that the developer 

has determined that the product 

satisfies the Agency’s safety 

requirements. Such information can 

facilitate acceptance by importing 

countries. Absent such a posting, the 

field for EPA information would be 

blank, and importers might question the 

regulatory status of the product in the 

United States. In addition, EPA 

considers that such a list may be useful 

to the Agency for ensuring enforcement 

and compliance with FIFRA regulations 

because it will enable compliance 

personnel to ascertain the exemption 

status of products encountered in 

distribution and trade channels. 

2. Exemption by Agency 

determination. If a PVCP-PIP does not 

satisfy a particular criterion under 

paragraph (1) (i.e., § 174.27(a)(1), (b)(1), 

or (c)(1)), EPA proposes that as an 

alternative route to exemption, the 

product developer would submit data or 

other information to the Agency to 

demonstrate that a particular PVCP-PIP 

meets paragraph (2) of that criterion 

(i.e., it meets § 174.27(a)(2), (b)(2), or 

(c)(2), respectively). In addition, as part 

of this submission, a developer would 

also include a certification as to any 

determination that the product meets 

§ 174.27(a)(1), (b)(1), and/or (c)(1), as 

appropriate. During its review under 

§ 174.27(a)(2), (b)(2), and/or (c)(2), EPA 

would not review the developer’s 

determination that the product met any 

criterion under § 174.27(a)(1), (b)(1), or 

(c)(1). 

EPA expects that in many instances 

developers would have most, if not all 

the information that would need to be 

included in any exemption submission 

under §§ 174.27(a)(2), (b)(2), or (c)(2) 

because it would have been gathered in 

the course of product development or 

for submission to USDA/APHIS as part 

of a petition for determination for nonregulated status. EPA will consult with 

USDA in evaluating whether a PVCPPIP meets the conditions for an Agencydetermined exemption. EPA is 

proposing that information supporting 

the submission be maintained as records 

that will be available for EPA inspection 

as necessary for the duration of time 

that the PVCP-PIP is sold or distributed. 

EPA will evaluate the information 

contained in the submission and 

publish a notice allowing the public to 

comment on the Agency’s determination 

that a product meets § 174.27(a)(2), 

(b)(2), and/or (c)(2), as appropriate. EPA 

is providing such a public comment 

period because even though the public 

will have had the opportunity to 

comment through this proposal on the 

appropriateness of the criteria in 

§ 174.27(a)(2), (b)(2), and (c)(2), the 

public would not otherwise have an 

opportunity to comment on whether a 

particular PVCP-PIP meets these 

criteria, given that these determinations 

depend on a case-by-case analysis of 

several types of information. 

The Agency plans to publish a 

Federal Register notice announcing its 

determination that a PVCP-PIP meets 

§ 174.27(a)(2), (b)(2), and/or (c)(2), and if 

no adverse comments are received 

during the comment period, the 

Agency’s decision will be considered 

final, and EPA will publish no further 

notice. Based on its experience with 

EUP notices, EPA expects that, in 

general, determinations that a PVCP-PIP 

qualifies for exemption will be 

noncontroversial and generate no 

adverse comments. However, in the case 

of adverse comments, EPA would 

publish a subsequent Federal Register 

notice announcing its final 

determination and address all public 

comments. EPA would prefer criteria in 

§ 174.27(a)(2), (b)(2), and (c)(2) that 

would allow the public and PVCP-PIP 

developers to readily predict the 

outcome of an Agency review. Such 

criteria would reduce regulatory 

uncertainty in PVCP-PIP development 

and decrease the time EPA would need 

to evaluate the data/information 

necessary to make a determination that 

a PVCP-PIP meets a given criterion. 

However, using criteria for which 

determinations can be readily predicted 

might reduce the number of PVCP-PIPs 

that would qualify for exemption. EPA 

tried to balance these concerns and 

proposed multiple options when the 

Agency was unsure how to resolve this 

dilemma. 

However, EPA does not believe that 

the considerations underlying its 

decisions to grant the public a further 

opportunity to comment on the 

Agency’s decision apply in cases where 

the Agency rejects a submission for an 

exemption. Accordingly, if EPA 

determines that the product fails to meet 

one or more of the exemption criteria, 

EPA will provide notice to the applicant 

of its decision on the submission and 

that a registration would be required for 

the PVCP-PIP before the PVCP-PIP 

could be sold or distributed. The 

product developer may then submit an 

application for registration to the 

Agency. EPA would evaluate such 

PVCP-PIPs under the existing 

registration process and could 

implement conditions of use as 

appropriate. 

B. Key Scientific Issues Associated with 

the Proposed Exemption Criteria under 

§ 174.27 

Several scientific questions 

concerning risk issues associated with 

PVCP-PIPs have been identified: 

• What is the potential for a PVCPPIP to endow plants with characteristics 


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1 In the context of the phrase ‘‘wild and weedy’’

relatives/plants used throughout this preamble, 

EPA considers weedy plants to be those with the 

characteristics of weeds, i.e., those that are 

considered undesirable, unattractive, or 

troublesome, especially when growing where they 

are not wanted. Wild plants are those that occur, 

grow, and live in a natural state and are not 

domesticated, cultivated, or tamed. EPA considers 

a naturalized population to be an enduring 

population of domesticated plants that grows in 

wild (non-cultivated) areas. EPA considers a native 

plant population to be one that originates in a 

particular region or ecosystem. 

that could disrupt the existing network 

of ecological relationships in managed, 

semi-managed, or natural ecosystems, 

e.g., through gene transfer to wild or 

weedy1 relatives? This issue is 

addressed at proposed § 174.27(a) and is 

referred to as ‘‘weediness’’ for the 

purposes of this discussion. 

• What is the potential for 

interactions between a PVCP-PIP and an 

infecting virus to affect plant virus 

epidemiology or pathogenicity? This 

issue is addressed at proposed 

§ 174.27(b) and is referred to as ‘‘viral 

interactions’’ for the purposes of this 

discussion. 

• What is the potential for exposure 

of humans or nontarget organisms to 

PVC-proteins with novel toxic or 

allergenic properties? This issue is 

addressed at proposed § 174.27(c) and is 

referred to as ‘‘protein production’’ for 

the purposes of this discussion. 

These three questions are addressed 

below under the headings of weediness, 

viral interactions, and protein 

production, respectively. 

C. Weediness 

1. Scientific issues. In evaluating 

whether a PVCP-PIP could alter 

ecological relationships among plants, 

EPA considered two primary issues: (1) 

whether the PVCP-PIP could endow a 

transgenic plant itself with an increased 

ability to spread into natural or semimanaged habitats and (2) whether the 

transfer of a PVCP-PIP from a transgenic 

plant into wild or weedy relatives could 

endow the wild or weedy relative with 

increased competitive ability and thus 

disrupt ecological relationships. Gene 

transfer among sexually compatible 

plants is a natural phenomenon that 

EPA does not consider to be an 

environmental risk per se. Whether the 

transfer of a PVCP-PIP could 

significantly disrupt ecological 

relationships in specific instances 

depends on all of the following 

considerations: First, does the crop 

plant containing the PVCP-PIP have 

wild relatives with which it is able to 

hybridize in nature? If it does not, there 

can be no gene transfer. Second, if there 

are sexually compatible relatives, is the 

gene conferring virus resistance likely to 

become stable in the population? Third, 

is the stable introduction of a PVCP-PIP 

into the plant population (i.e., 

introgression) likely to cause the 

population to become more weedy/ 

invasive or otherwise alter its 

competitive ability, thereby significantly 

changing the population dynamics of 

the plant community? The 2005 SAP 

concurred that these are important 

considerations for PVCP-PIPs by noting 

that an ‘‘important ecological risk 

associated with gene flow from crop 

plants into their wild relatives is that 

the acquisition of crop genes might 

substantially alter the population 

dynamics of the wild plant. In 

particular, a transgene introgressed from 

the crop relative into a wild population 

might allow the wild species to persist 

in larger populations across a larger 

geographic range, or in a wider range of 

habitats. Collectively these changes in 

population dynamics can be considered 

‘increased weediness’. The probability 

that a particular transgene will lead to 

increased weediness depends on the 

phenotype conferred by the transgene 

and on the ecological factor(s) currently 

limiting the size or distribution of the 

wild species. In particular, if the 

transgene alters plant response to the 

ecological factor limiting population 

size, then population dynamics may be 

affected. For PVCP-PIPs, the relevant 

consideration is whether virus 

resistance (conferred by the PVCP-PIP) 

leads to changes in the size or 

distribution of wild plant species with 

the PVCP-PIP’’ (Ref. 11). 

i. Likelihood that a crop plant 

containing a PVCP-PIP could itself 

disrupt ecological relationships. In 

considering whether a PVCP-PIP could 

affect the ability of a plant to spread into 

natural or semi-managed habitat at the 

margins of cultivated fields, i.e., to form 

feral or naturalized populations, the key 

consideration is whether viral infection 

is currently limiting the ability of 

agricultural crops to do so. The 2005 

SAP pointed out that PVCP-PIPs ‘‘are 

developed when virus infection of a 

crop reduces the crop yield, suggesting 

that virus infection is quite likely in 

naturalized populations of the crop as 

well’’ (Ref. 11). However, virus infection 

in crop plants does not necessarily limit 

the spread of the crop into natural or 

semi-managed areas. As the 2005 Panel 

also noted, ‘‘little is known about factors 

controlling population size in plant 

populations in general, including those 

that are currently stable, as well as those 

that are currently weedy or invasive’’

(Ref. 11). Few published studies are 

available that evaluate this question 

directly, perhaps due to the general 

rarity of negative results in scientific 

literature. However, one study did find 

virus infection to have little effect on an 

agricultural crop. Field experiments 

with transgenic virus-resistant sugar 

beets revealed no competitive advantage 

(measured as seedling emergence and 

biomass production) between the 

transgenic and susceptible control lines 

(Ref. 12). 

Although virus infection has been 

shown to negatively impact growth and/ 

or reproduction of some natural plant 

communities (discussed below in Unit 

III.C.1.ii.), EPA recognizes that there is 

reason to question whether the situation 

would be different for crop plants. The 

National Research Council (NRC) noted 

in 1989 that most naturalized, 

domesticated crops generally are unable 

to effectively compete with wild species 

in natural ecosystems and have not been 

known to acquire this ability with the 

type of single-gene traits commonly 

introduced through genetic modification 

(Ref. 13). The 1989 NRC report went on 

to note that plant breeders have 

capitalized for decades on the fact that 

relatively minor genetic changes can 

produce plants with altered ecological 

properties, but the addition of pest 

resistant traits has not been known to 

result in increased weediness of widely 

used crops (Ref. 13). A 1989 survey of 

the weedy characteristics of crop versus 

weed species showed that weeds 

possess significantly more weedy 

characteristics on average than do crop 

plants (Ref. 14). For domesticated crops, 

the traits that make them useful to 

humans also reduce their competitive 

ability in nonagricultural habitats. Crops 

that have been subjected to long-term 

breeding (e.g., corn and soybeans) are 

unlikely to possess characteristics that 

would allow the plant to compete 

effectively outside of managed 

ecosystems. Domesticity arises because 

intensive breeding efforts seek to 

eliminate many characteristics of the 

crop plant that would enhance 

weediness (e.g., seed shattering, thorns, 

seed dormancy, and bitterness). For 

example, lack of seed shattering and 

seed dormancy greatly reduces the 

ability of an annual crop to persist 

without human intervention. Highly 

domesticated crops such as corn are 

thus unlikely to survive for multiple 

generations outside agricultural fields 

no matter what transgenic trait they 

contain, including virus resistance (Ref. 

15). 

However, some crop species, e.g., 

cranberry and blackberry may have 

more similarities to their wild relatives 

than highly domesticated crops such as 

corn or soybean. As noted by the 2005 


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SAP, ‘‘Determining whether a particular 

crop can naturalize and then spread as 

a weedy species is difficult to ascertain 

from the literature and determining the 

probability that a crop will be more 

weedy or invasive if it contains a PVCPPIP is even more difficult’’ (Ref. 11). 

Such determinations may therefore need 

to rely on information not available in 

public literature as part of a risk 

assessment for a particular plant. Plants, 

such as forest trees, that may grow for 

many years in natural environments or 

in very close proximity to natural 

environments present additional 

difficulty in evaluating and managing 

risks (Ref. 16). The period of time over 

which such plants would persist is 

significantly longer than for annual, 

short-lived species. Individual plants 

will therefore experience a much wider 

range and variety of stress conditions, 

enemy attacks, and climate change, 

making predictions about naturalization 

potential with acquired virus resistance 

particularly challenging. 

Thus, although EPA believes that 

many crop species are unlikely to 

disrupt ecological relationships through 

acquisition of a PVCP-PIP, the available 

information is insufficient to support 

the general conclusions that EPA would 

need to make for a categorical 

exemption of PVCP-PIPs. EPA would 

need to conclude that there is a low risk 

that acquisition of a PVCP-PIP would 

significantly affect the competitiveness 

of any of the plants currently grown as 

crops and that none of these crop 

species would significantly disrupt 

ecological relationships when modified 

to contain a PVCP-PIP. Therefore, the 

Agency believes that it is necessary to 

evaluate each plant species 

independently to consider whether it is 

likely to establish weedy or invasive 

populations outside of agricultural 

fields in the United States and thereby 

potentially significantly disrupt 

ecological relationships if it becomes 

virus resistant due to a PVCP-PIP. 

Factors likely to influence this 

determination cannot be readily 

distilled into a straightforward criterion 

suitable for a categorical exemption. 

ii. Likelihood that a crop plant 

containing a PVCP-PIP could 

significantly disrupt ecological 

relationships through gene transfer. The 

question of whether gene transfer from 

a crop to a wild or weedy relative could 

significantly disrupt ecological 

relationships is a more complicated 

question because a much broader range 

of potential plants may be involved 

when wild or weedy relatives are 

considered in addition to the crops 

themselves. The answer to this question 

depends first on the question of whether 

the transgenic crop plants could transfer 

a PVCP-PIP to other plant populations. 

This potential for transfer depends in 

part on the frequency of hybridization 

between domesticated species and their 

wild relatives. Hybridization is affected 

by the ability of plants to cross-pollinate 

which in turn is affected by their timing 

of reproductive viability and the 

proximity of the plants. Hybridization is 

also affected by the ability of pollen to 

fertilize recipient plants, the recipient 

plants to develop viable seeds, these 

seeds to germinate, and the seedlings to 

grow into viable adults (Ref. 17). In spite 

of these potential constraints, a survey 

of the world’s most important crops 

suggests that spontaneous hybridization 

of domesticated plants with wild 

relatives appears to be a general feature 

across at least a portion of the 

worldwide geographic area over which 

each is cultivated (Refs. 18 and 19). The 

ability to cross crops with wild relatives 

(which may not necessarily occur where 

the crop is grown) is also the basis of 

many traditional breeding techniques 

that are used for virtually all crops (Ref. 

20). 

Whether virus infection limits the 

growth and/or reproductive ability of 

wild or weedy plant populations is 

more difficult to answer generically for 

all plants in all ecosystems. Viruses are 

pervasive in many natural plant 

populations (Refs. 21, 22, 23, and 24), 

although a comprehensive body of 

literature on the effect of viruses in 

weed species is lacking. According to 

the 2004 SAP, ‘‘Our knowledge about 

the effect of virus infection on non-crop 

plants is quite limited’’ (Ref. 25). Some 

published studies report that virus 

infection can have little or no effect on 

the plants. For example, a survey of 

Plantago species in England showed 

that although 92 of 144 plants were 

infected with one or more viruses, most 

of the plants showed no obvious disease 

symptoms (Ref. 23). A literature review 

of the role of weeds in the occurrence 

and spread of plant virus diseases 

describes several cases where viruses 

significantly damage certain crops but 

have little effect on their weed hosts 

(Ref. 26). 

Other published studies have reported 

that infection reduces plant growth and/ 

or fecundity. For example, naturally 

occurring tobacco leaf curl virus 

infection increases mortality and has 

negative effects on growth and seed 

output in plants from wild populations 

of the flowering perennial plant 

Eupatorium chinense (Ref. 27). 

Greenhouse experiments with this same 

plant under two irradiance levels 

showed that virus infection did not 

affect survivorship under high-light 

conditions but caused severe damage 

under low-light conditions (Ref. 28). 

Vegetative growth and flower 

production of purslane (Portulaca 

oleracea) was also reduced when plants 

were inoculated with cucumber mosaic 

virus (Ref. 29). Field experiments 

showed that wild cabbage plants 

(Brassica oleracea) inoculated with 

turnip mosaic virus or turnip yellow 

mosaic virus have reduced survival, 

growth, and reproduction (Ref. 30). 

Such experiments suggest that viruses 

can sometimes reduce individual plant 

growth and/or fecundity when infection 

occurs. However, individual-level 

effects are insufficient to understand 

population-level processes. For 

example, even if virus disease 

significantly affected individual plant 

fitness, a decline in individual-plant 

fitness might reduce competition such 

that uninfected plants could increase 

reproductive output, thereby mitigating 

any population-level effects (Ref. 31). 

It can be difficult to predict the actual 

impact on overall plant population 

dynamics that would result from 

acquisition of virus resistance by plants 

that are in some way negatively affected 

by virus infection. EPA is not aware of 

any published study that has directly 

examined this question by, for example, 

purposefully freeing a plant species 

from virus infection and investigating 

the resulting population dynamics of 

infected versus uninfected plants. The 

2004 SAP was also unaware of any such 

study, but offered that ‘‘[b]ased on 

knowledge obtained from observation of 

cultivated crops in the agroecosystem, 

the majority of the Panel concluded that 

it would be unlikely that a plant 

population freed from viral pressure 

would give a plant species a competitive 

advantage’’ (Ref. 25). Some members of 

the 2005 SAP agreed with the 2004 SAP, 

while ‘‘[o]ther members of the current 

[2005] SAP believed, based on new 

information (Fuchs et al. 2004; Sukopp 

et al., 2005) not available to the 2004 

Panel, as well as EPA indicating a lack 

of data on this topic, that concluding 

that viruses typically have no effect on 

their wild plant hosts is not accurate. 

Because of the differing opinions among 

the current [2005] Panelists, and the 

general paucity of data, the Panel 

cautioned that further research is 

needed to provide stronger support to 

this particular issue’’ (Refs. 11, 32, and 

33). EPA also notes that evaluating 

impacts on plant population dynamics 

is further complicated because in 

certain cases gene transfer of a PVCPPIP to wild or weedy relatives might 

potentially be desirable. For example, 

an invasive virus species might be 


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effectively controlled through broad 

acquisition of resistance by plant 

species susceptible to the virus. 

Controlling disease outbreaks in 

perennial agricultural plants and trees 

could be significantly aided by reducing 

viral load in the environment through 

such approaches. 

A few studies are available that are 

relevant to the question of whether 

acquisition of virus resistance could 

affect plant population dynamics. These 

studies show that in some cases virus 

infection can have such effects, 

suggesting that acquired virus resistance 

might as well. For example, infection 

with alfalfa mosaic virus substantially 

diminished the ability of certain medic 

cultivars to compete with other species 

such as capeweed in grazed pasture 

swards, both directly by decreasing the 

competitive ability of infected plants, 

and indirectly by altering the 

proportions in which the species 

germinated (Ref. 34). In another 

example of virus infection affecting 

plant population dynamics, growth 

analysis of Eupatorium makinoi 

revealed that plants naturally infected 

with a geminivirus had significantly 

reduced stem growth and plant height, 

along with decreased flowering and 

survivorship. This study suggests that in 

spite of the long-term coexistence of the 

virus and Eupatorium makinoi, such 

negative fitness attributes have a 

significant impact on at least some local 

plant populations in this species (Ref. 

35). 

Although relatively little research has 

been published regarding how plant 

population dynamics are directly 

influenced by virus infection, such 

results as described in the previous 

paragraph provide some support for the 

premise that virus resistance might be 

an important ecological fitness 

characteristic. At least some plant 

populations acquiring virus resistance 

might in some instances be able to better 

compete against other species (Ref. 36) 

and/or spread to habitats previously 

unsuitable because of the presence of 

the virus (Ref. 37). For example, a broad 

survey of geographic data on plant 

associations with viruses from 

published compendia and governmental 

or academic databases showed that 

plants were infected by 24% fewer 

viruses in their naturalized ranges than 

in their native ranges, supporting the 

hypothesis that the impact of invasive 

plants results in part from reduced 

natural enemy (e.g., virus) attack (Ref. 

38). On the other hand, enemy release 

is only one of many hypotheses that 

could explain the abundance and/or 

impact of an invasive plant (Ref. 39). In 

addition, a few published studies have 

reported that in certain instances virus 

infection can increase plant fitness, 

suggesting that acquisition of virus 

resistance might decrease plant fitness. 

For example, infection by barley yellow 

dwarf virus was found in at least 1 year 

to increase the fitness of the host plant 

green foxtail (Setaria viridis) by 

approximately 25% (Ref. 40). In some 

cases, plants might be more attractive to 

herbivores when not infected by viruses, 

as was found to be the case for dusky 

coral pea (Kennedya rubicunda; Ref. 

41). In this experiment, caged rabbits 

presented with a mixture of carrots and 

powdered plant extract grazed the 

mixture made from virus-free plant 

material at twice the rate as plant 

material infected with Kennedya yellow 

dwarf virus due presumably to greater 

palatability. In general, negative fitness 

attributes would be expected to be 

selected against in populations. 

Nevertheless, such considerations might 

be important in certain instances, e.g., 

when evaluating possible effects on 

endangered species. 

EPA believes it likely that many of the 

potential PVCP-PIP/plant combinations 

pose a low risk of disrupting the 

existing network of ecological 

relationships in semi-managed or 

natural ecosystems. Multiple conditions 

must be met to pose a higher level of 

risk, i.e., hybridization with a wild 

relative must occur, introgression of the 

gene must occur, and acquired virus 

resistance must confer an advantage (or 

disadvantage) to the recipient plant 

sufficient to alter plant population 

dynamics. Nevertheless, the research 

discussed above showing that in some 

cases viruses can affect plant population 

dynamics for at least some plants 

highlights the difficulty in drawing a 

general conclusion as to whether all 

PVCP-PIP/plant combinations are likely 

to pose a low risk of significantly 

disrupting existing ecological networks. 

Virtually any crop could be modified to 

contain a PVCP-PIP, including less 

domesticated forage crops and trees, and 

such a wide range of plants will be 

associated with a concomitantly wide 

range of characteristics and behaviors. 

Ecosystems are highly complex and 

variable, and some of the factors that 

limit fitness of a given plant species can 

be subtle and are not well understood 

(Ref. 15). Consequently, EPA does not 

believe that the available body of 

evidence would currently support a 

definitive conclusion for all PVCP-PIPs 

that the potential transfer to wild or 

weedy relatives presents a low risk of 

significantly altering the network of 

ecological relationships in semimanaged or natural ecosystems. 

Information may be available to 

evaluate the likelihood of acquired virus 

resistance impacting a particular plant 

species or population. However, the 

existing body of literature currently 

does not appear sufficient to describe 

any set of circumstances that would 

predict for the wide variety of possible 

PVCP-PIP/plant combinations whether 

introgression of the PVCP-PIP into a 

wild or weedy relative could change the 

population dynamics of the recipient 

plant and through this route potentially 

affect ecological relationships with 

other plants and other organisms in the 

community. For example, it is not 

possible to predict a priori whether a 

possible fitness advantage that 

individual plants might acquire with a 

PVCP-PIP would make the plant 

population better able to compete 

against other species. Whether 

population dynamics would be affected 

and ecological relationships could be 

disrupted in a given circumstance is 

dependent on multiple, interacting 

factors. In some instances, a weight-ofevidence, case-by-case review of 

information such as experimental data 

might allow such a determination; 

however, general knowledge of factors 

likely to influence population dynamics 

cannot be readily distilled into a 

straightforward criterion suitable for a 

categorical exemption. 

2. Proposed exemption criterion. EPA 

is proposing § 174.27(a) based on a set 

of considerations articulated by the 

2005 SAP to identify plants that would 

not pose concerns associated with 

increased weediness of either the crop 

plant itself or any sexually-compatible 

wild relatives, if the crop plant were to 

contain a PVCP-PIP. Section 

174.27(a)(1) is a categorical exemption 

criterion for a subset of PVCP-PIPs, i.e., 

a list of plants that have already been 

determined by the Agency to be low risk 

with respect to concerns associated with 

weediness irrespective of the particular 

PVCP-PIP the plants might contain. 

Section 174.27(a)(2) is a conditional 

exemption criterion based on Agency 

review of whether a particular plant/ 

PVCP-PIP combination poses low risk 

with respect to concerns associated with 

weediness. Both parts of § 174.27(a) are 

discussed in more detail in Units 

III.E.1.iii. and III.E.1.iv. below. Note that 

a PVCP-PIP qualifies for exemption 

based in part on its presence in a 

particular crop species. The record on 

which this proposed exemption is based 

is not currently broad enough to support 

an exemption for a PVCP-PIP in another 

species if that species has not been 

evaluated for concerns associated with 

weediness when it contains a particular 


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virus-resistant trait. A PVCP-PIP that 

has been moved into another species 

does not qualify for the exemption 

unless the recipient plant appears on 

the list in § 174.27(a)(1). Such a PVCPPIP would either need an individual 

exemption determination under 

§ 174.27(a)(2) or a registration in order 

to be sold or distributed. 

i. Proposed categorical exemption 

criterion in § 174.27(a)(1). As articulated 

above, EPA does not believe it can 

propose a categorical exemption based 

on whether a PVCP-PIP/plant 

combination is likely to result in 

changes in plant population dynamics 

because this endpoint cannot easily be 

predicted based on straightforward 

characteristics of the PVCP-PIP and/or 

plant. However, EPA believes that a 

criterion for a categorical exemption 

could be developed based on evaluation 

of individual crop species for their 

potential to naturalize and invade 

natural ecosystems, including with 

acquisition of a PVCP-PIP and for the 

existence of wild or weedy relatives that 

could acquire a PVCP-PIP through gene 

flow. Certain plants are expected to pose 

low risk with respect to concerns 

associated with weediness regardless of 

any particular PVCP-PIP that the species 

contained. However, for the categorical 

exemption, the Agency is attempting to 

identify those situations where no caseby-case review is necessary to conclude 

that a PVCP-PIP would present a low 

risk of causing adverse effects. In such 

situations, a product developer could 

use a clearly defined criterion to make 

a determination of status. Based on 

these considerations, EPA has 

developed a list of plants that the 

Agency proposes a developer could use 

to self-determine whether § 174.27(a) is 

met. 

A PVCP-PIP would meet proposed 

§ 174.27(a) under § 174.27(a)(1) if the 

plant containing the PIP is one of the 

following: Anthurium (Anthurium spp.), 

asparagus (Asparagus officinale), 

avocado (Persea americana), banana 

(Musa acuminata), barley (Hordeum 

vulgare), bean (Phaseolus vulgaris), 

cacao (Theobroma cacao), carnation 

(Dianthus caryophyllus), chickpea 

(Cicer arietinum), citrus (Citrus spp., 

e.g., Citrus aurantifolia, Citrus limon, 

Citrus paradisii, Citrus sinensis), coffee 

(Coffea arabica and Coffea canephora), 

corn (Zea maize), cowpea (Vigna 

unguiculata), cucumber (Cucumis 

sativus), gerbera (Gerbera spp.), 

gladiolus (Gladiolus spp.), lentil (Lens 

culinaris), mango (Mangifera indica), 

orchids (Orchidaceae), papaya (Carica 

papaya), pea (Pisum sativum), peanut 

(Arachis hypogaea), pineapple (Ananas 

comosus), potato (Solanum tuberosum), 

soybean (Glycine max), starfruit 

(Averrhoa carambola), sugarcane 

(Saccharum officinarum), or tulips 

(Tulipa spp.). 

EPA developed this list of plants after 

consultations with both the 2004 and 

2005 SAPs. The 2004 SAP 

recommended a longer list of plants, 

chosen initially based on the 

presumption that they had no wild or 

weedy relatives in the United States. 

However, the 2005 SAP noted that the 

longer list of plants recommended by 

the 2004 SAP clearly contained ‘‘some 

species that form viable crop-wild 

hybrids...’’ (Ref. 11). Recognizing that 

much of the most useful information is 

not likely to be found in the literature, 

‘‘the Panel recommended consulting 

agronomists, breeders, and/or ecologists 

with specialized expertise before 

including any crop on a list of exempt 

species’’ (Ref. 11). The 2005 Panel also 

recommended a specific set of 

conditions that each species would have 

to meet based on the advice of such 

experts (i.e., agronomists, breeders, and/ 

or ecologists with specialized expertise) 

if it were to be placed on the list: 

1. A crop should be included on the 

exempt list if it forms no viable hybrids with 

wild or weedy relatives anywhere in the US... 

2. A crop should...be included on the 

exempt list only if it is [not] currently weedy 

or invasive... 

3. A crop should be included on the 

exempt list if... it will not establish weedy or 

invasive populations if it becomes virus 

resistant (due to a PVCP-PIP)... 

4. If a PVCP-PIP crop has the potential to 

naturalize, but the PVCP-PIP transgene is in 

biocontainment and/or biomitigation 

constructs that are stacked such that escapes 

from cultivation are too unfit to compete 

with the wild type, a consensus of breeders, 

agronomists, and ecologists, or others with 

experience with the species could advise 

addition to the list (Ref. 11). 

EPA believes that the first three 

conditions proposed by the 2005 SAP 

are useful factors in evaluating whether 

a plant warrants inclusion on the list in 

§ 174.27(a)(1). EPA considered each of 

these factors when evaluating each of 

the plants currently on the list in 

proposed § 174.27(a)(1). However, EPA 

also recognizes that plants that do not 

strictly meet condition 1 as laid out by 

the SAP may nevertheless be 

determined to pose low risk with 

respect to weediness concerns after a 

case-by-case review of the plants’ traits 

and consideration of the whole range of 

factors that affect weediness. For 

example, corn may not meet the first 

condition above as articulated by the 

SAP if it proves to in fact have wild 

relatives in some region of the United 

States with which it can form viable 

hybrids. However, as discussed below, 

EPA does not believe that the 

characteristics of the wild relatives or 

the hybrids that could be formed suggest 

any reason to suspect acquired virus 

resistance would change the weediness 

potential of corn, the hybrid, or the wild 

relative, and EPA therefore proposes to 

include corn on the list. Thus, in 

practice EPA considers the 2005 SAP’s 

first three conditions as a useful guide 

of the factors that should be taken into 

account in evaluating whether to 

include a plant on the list. However, 

EPA believes that relying on a strict 

interpretation of these conditions would 

exclude many plants containing PVCPPIPs that meet FIFRA’s low risk 

standard. The 2005 SAP itself suggested 

that some flexibility of interpretation 

might be appropriate. Although the 

Panel used the phrase ‘‘no viable 

hybrids’’ in condition 1, the Panel 

elsewhere recommended against 

granting exemption to crops with 

‘‘sexually compatible wild relatives’’

where ‘‘sexually compatible refers to the 

possibility of having crop transgenes 

backcross and introgress into the 

relative; it does not refer to sterile 

hybrids’’ (Ref. 11). 

Although EPA considered the first 

three conditions proposed by the 2005 

SAP in deciding whether to include a 

particular plant species on the list in 

§ 174.27(a)(1), EPA believes that the 

fourth condition as articulated would be 

inappropriate for these purposes. A 

biocontainment and/or biomitigation 

construct would be associated with a 

particular PVCP-PIP, not a particular 

plant species. The intent of 

§ 174.27(a)(1) is to list species that 

would not present concerns related to 

weediness regardless of the particular 

PVCP-PIP that the species contained. 

EPA believes that construct-specific 

considerations could be taken into 

account under an Agency review 

procedure such as that described below 

in Unit III.C.2.iii. 

The Panel recommended ‘‘consulting 

agronomists, breeders, and/or ecologists 

with specialized (taxon-specific) 

expertise on weedy populations before 

including any crop on a list of exempt 

species’’ because this information ‘‘is 

difficult to ascertain from the literature 

and determining the probability that a 

crop will be more weedy or invasive if 

it contains a PVCP-PIP is even more 

difficult.’’ Likewise, the Panel indicated 

‘‘[i]t is very difficult to identify crops 

that have no sexually compatible wild 

or weedy relatives in the US or its 

possessions and that do not become 

weedy or invasive themselves. This 

information is unique to each crop, is 

often not published, and is often known 

only by the agronomists, breeders, and 


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ecologists working with the specific taxa 

in question’’ (Ref. 11). EPA agrees that 

such information is difficult to obtain 

from the literature and therefore relied 

on written consultation with such 

experts in evaluating whether the three 

conditions proposed by the 2005 SAP 

had been met for a particular crop 

species. 

In consulting with experts for a 

particular crop, EPA asked at least three 

individuals a series of questions 

designed to address the issues identified 

by the 2005 SAP as relevant for 

evaluating whether a PVCP-PIP would 

be low risk with respect to concerns 

associated with weediness if it were to 

be found in the particular species. 

Specifically, EPA wanted to know: 

• Does this crop form viable hybrids in 

nature (i.e., without human 

intervention) with wild or weedy 

relatives in the United States (including 

Puerto Rico, the Virgin Islands, Guam, 

the Trust Territory of the Pacific Islands, 

and American Samoa)? 

If yes, what species are they? Which 

of these species are themselves 

commercially grown crops? What is the 

frequency of hybrid production? Have 

hybrids demonstrated enhanced fitness 

(vigor) relative to parental varieties? Can 

the hybrids reproduce asexually? Are 

the hybrids sexually fertile? 

If hybrids are sexually fertile, will 

they outcross or only backcross with the 

crop parent? How does the phenology of 

the crop species compare with the 

phenology of plant(s) with which it is 

sexually compatible? Are there any 

other attributes of these species that 

may enhance or inhibit sexual 

reproduction and species out-crossing? 

• Is this crop known to become feral 

or easily spread into non-crop areas in 

the United States (including Puerto 

Rico, the Virgin Islands, Guam, the 

Trust Territory of the Pacific Islands, 

and American Samoa)? If yes, have 

escaped plants formed reproducing and 

sustaining populations in non-crop 

areas? Where has this been known to 

happen? With what frequency is this 

likely to occur? Have feral populations 

required weed management activity? 

• How likely is it that this crop would 

become feral or easily spread into noncrop areas if it acquired transgenic 

resistance to one or more viruses? What 

is the basis for your answer? 

EPA focused these questions on ‘‘noncrop areas’’ to emphasize that the key 

consideration is a crop’s behavior in 

natural settings. EPA recognizes that 

most crops within agricultural fields 

form volunteer populations, where 

propagules of the crop from the 

previous rotation grow in the 

subsequent crop rotation. The Agency 

did not consider behavior in crop areas 

when evaluating the crops for inclusion 

on the list at proposed § 174.27(a)(1). 

The responses to specific Agencyposed questions received from these 

expert consultations are available in the 

docket for this proposed rule (Ref. 42). 

EPA considered the experts’ responses 

in conjunction with other information 

when determining whether to list a crop 

at proposed § 174.27(a)(1), as discussed 

below. Crops that EPA evaluated but did 

not include in the proposed list for one 

reason or another are discussed in Unit 

VII where comment on these crops is 

specifically requested. 

EPA notes that the 2005 SAP also 

suggested the Agency ‘‘consider the 

geographic distribution of crops and 

their wild relatives when considering 

potential exemptions’’ (Ref. 11). 

Although this is a potential option the 

Agency could pursue, a number of 

considerations limit the utility of using 

the potential for geographic isolation in 

determining whether a plant could be 

included on the list in § 174.27(a)(1). 

For example, EPA would need to 

consider carefully whether such 

isolation is likely to remain throughout 

the commercial life of the PVCP-PIP. 

Such isolation could occur if the crop 

containing the PVCP-PIP would not be 

commercially viable in the areas where 

wild relatives occur given biological 

considerations that are unlikely to 

change. However, geographic isolation 

could also be due to factors that may 

change throughout the commercial life 

of a PVCP-PIP, e.g., individual farmer 

choices of which crops to plant. Because 

of such considerations, EPA anticipates 

that it would only be able to support an 

exemption dependant on geographic 

restrictions where biological or similar 

factors provide assurance that the 

geographic isolation will remain 

constant during the entire commercial 

life of the PVCP-PIP. 

The next several Subunits summarize 

EPA’s conclusions to include the crops 

listed at proposed § 174.27(a)(1) based 

on consideration of the conditions 

suggested by the 2005 SAP and their 

recommendation that evaluation of 

these conditions be done in consultation 

with breeders, agronomists, and 

ecologists familiar with the particular 

species. The analyses below indicate 

that there is an extremely low 

probability that virus resistance 

conferred through a PVCP-PIP in any of 

these plants would significantly alter 

existing plant population dynamics or 

existing ecological relationships. The 

list is straightforward, providing an 

easy-to-understand criterion. 

Accordingly, EPA is proposing that a 

developer may self-determine whether a 

PVCP-PIP meets this criterion, i.e., 

whether the plant containing the PVCPPIP is on the proposed list, because no 

further data or information would be 

needed to evaluate whether ecological 

relationships could be disrupted 

through increased weediness when the 

plant modified to contain the PVCP-PIP 

is on the list. 

a. Anthurium. EPA proposes that 

anthurium (Anthurium spp.) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

anthurium experts. These consultations 

indicate that anthurium meets the three 

conditions outlined above by the SAP: 

It does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make anthurium 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘The commercial species 

[of] Anthurium (Anthurium 

schezerianum and Anthurium 

andraenum) have been grown outdoors 

since the early 1900’s in semi-tropical 

and tropical areas of the US and there 

are no records of any commercial 

species escaping and becoming feral 

into non-crop areas. There is no reason 

to believe that acquiring transgenic 

resistance to one or more viruses would 

increase the ability of plants to become 

feral or easily spread into non-crop 

areas’’ (Ref. 42). EPA therefore believes 

that anthurium meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

b. Asparagus. EPA proposes that 

asparagus (Asparagus officinale) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

asparagus experts. These consultations 

indicate that asparagus meets the three 

conditions outlined above by the SAP. 

One, it does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature. One expert said, ‘‘Although 

volunteer asparagus plants may grow 

‘‘wild’’ (i.e., not intentionally 

cultivated), they are not typically 

considered to be weeds. There are 

several horticultural varieties of 

asparagus, which could potentially be 

cross-pollinated. However, considering 

that asparagus is insect pollinated, this 

is likely to occur only in the rare 

situation where an asparagus grower 

also is growing horticultural varieties’’

(Ref. 42). Second, the experts agreed 

that asparagus is not currently weedy or 

invasive outside of agricultural fields in 


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the United States. Two of the three 

experts indicated that asparagus can 

infrequently become feral. However, 

‘‘[a]sparagus is not typically considered 

to be a weedy species. In addition, since 

asparagus has separate male and female 

plants, it is considerably more difficult 

for ‘‘wild’’ populations to become 

established. Asparagus is also a 

relatively slow growing plant such that 

eradication (if necessary) would not be 

particularly onerous’’ (Ref. 42). Third, 

these experts agreed that it is unlikely 

that acquisition of virus resistance 

would make asparagus weedy or 

invasive. For example, one expert 

stated, ‘‘I have worked with this crop 

since 1978 and in all those years, I have 

not observed asparagus to become easily 

spread at all in non-crop or crop areas. 

Although asparagus does rarely grow 

wild in some areas (usually the 

temperate zones) asparagus is a very 

poor competitor with weeds and other 

plants and asparagus requires much 

attention and cultural care to thrive. I 

have only viewed a very rare 

occassionaly [sic] plant along fence 

rows and they usually are very weak 

and non-vigorous. Acquired transgenic 

resistance would do nothing to affect 

asparagus to become feral’’ (Ref. 42). 

EPA therefore believes that asparagus 

meets the conditions recommended by 

the 2005 SAP for inclusion on the list 

and will present low risk with respect 

to weediness. 

c. Avocado. EPA proposes that 

avocado (Persea americana) be included 

on the list in § 174.27(a)(1) based on 

EPA consultations with avocado 

experts. These consultations indicate 

that avocado meets the three conditions 

outlined above by the SAP: It does not 

have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make avocado weedy 

or invasive. All three experts contacted 

by EPA indicated agreement with these 

statements. For example, one expert 

stated ‘‘Transgenic resistance should not 

affect the likelihood of spread. Viral 

susceptibility is not an important factor 

limiting the plant’s ability to become 

feral’’ (Ref. 42). EPA therefore believes 

that avocado meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

d. Banana. EPA proposes that banana 

(Musa acuminata) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with banana experts. 

These consultations indicate that 

banana meets the three conditions 

outlined above by the SAP: It does not 

have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make banana weedy or 

invasive. All three experts contacted by 

EPA indicated agreement with these 

statements. For example, one expert 

stated ‘‘[i]t is highly unlikely that 

banana with acquired transgenic 

resistance would spread to non-crop 

areas because the probability of crossing 

is extremely small. Through vegetative 

propagation it will require man [sic] 

intervention just as non-transgenic 

plants’’ (Ref. 42). EPA therefore believes 

that banana meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

e. Barley. EPA proposes that barley 

(Hordeum vulgare) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with barley experts. These 

consultations indicate that barley meets 

the three conditions outlined above by 

the SAP: It does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature, it is not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make barley 

weedy or invasive, as viruses are not 

consistently associated with failure of 

barley to show any evidence of being 

weedy or invasive. Three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated that he believes the 

likelihood that barley would become 

feral or easily spread into non-crop 

areas if it acquired transgenic virus 

resistance is ‘‘negligible. Barley has 

been cultivated for decades in many 

U.S. environments, including 

environments that impose relatively 

mild disease pressure, particularly for 

viral diseases, such as the upper 

midwest and western states, and barley 

has not been able to establish itself in 

those regions as a feral species’’ (Ref. 

42). EPA notes that the 2005 SAP 

indicated that ‘‘barley can hybridize 

with Hordeum jubatum, which is a 

weed in the USA’’ (Ref. 11). However, 

three barley breeders consulted about 

this specific issue did not agree that 

hybridization was likely to occur. One 

stated, ‘‘In relation to Hordeum vulgare 

subsp. Vulgare (cultivated barley) 

Hordeum jubatum is in the tertiary 

genepool. This means crossability is 

extremely difficult event under 

laboratory conditions’’ (Ref. 42). A study 

that attempted to cross barley with two 

wild relatives, H. murinum L. and H. 

jubatum L., found that no hybridization 

occurred, even under favorable 

greenhouse conditions with forced 

pollination (Ref. 43). EPA therefore 

believes that barley meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

f. Bean. EPA proposes that bean 

(Phaseolus vulgaris) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with bean experts. These 

consultations indicate that bean meets 

the three conditions outlined above by 

the SAP. One, it does not have wild or 

weedy relatives in the United States 

with which it can form viable hybrids 

in nature. One expert mentioned that 

‘‘[h]ybrids between Phaseolus vulgaris 

and Phaseolus acutifolius (tepary bean) 

are only achieved through extensive 

crossing and embryo rescue and thus is 

highly unlikely to occur in nature’’ (Ref. 

42). Another expert said bean would 

‘‘only - but rarely - hybridize with wild 

vulgaris (only where wild vulgaris 

occur, generally not in [the United 

States] & there are often biological 

barriers to such occurring’’ (Ref. 42). 

Second, these experts agreed that bean 

is not currently weedy or invasive in the 

United States. Third, these experts 

agreed that it is unlikely that acquisition 

of virus resistance would make bean 

weedy or invasive. For example, one 

expert stated, ‘‘Viruses generally do not 

prevent susceptible beans from making 

a crop (just the yield and quality of the 

crop is greatly reduced’’ (Ref. 42). EPA 

therefore believes that bean meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

g. Cacao. EPA proposes that cacao 

(Theobroma cacao) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with cacao experts. These 

consultations indicate that cacao meets 

the three conditions outlined above by 

the SAP: It does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature, it is not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make cacao 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated that ‘‘cacao is difficult to 

cultivate, the seeds are very susceptible 

to desiccation, and germination must 

occur within a few days or the seed die 

[sic]’’ (Ref. 42). EPA therefore believes 

that cacao meets the conditions 


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recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

h. Carnation. EPA proposes that 

carnation (Dianthus caryophyllus) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

carnation experts. These consultations 

indicate that carnation meets the three 

conditions outlined above by the SAP. 

One, it does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature. Two, it is not currently weedy 

or invasive in the United States. One 

expert indicated that Arkansas and 

Massachusetts have populations of feral 

Dianthus caryophyllus. However these 

have not required management activity 

because ‘‘populations have remained 

small consisting of only a few plants’’

(Ref. 42). Three, there is no reason to 

believe that acquisition of virus 

resistance would make carnation weedy 

or invasive. One expert stated, ‘‘Most 

species of Dianthus are selfincompatible, and commercial 

selections of carnation require hand 

pollination, and set little viable seed. 

There is no record of carnation, D. 

caryophyllus, being naturalized or 

invasive in any part of the world’’ (Ref. 

42). EPA therefore believes that 

carnation meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

i. Chickpea. EPA proposes that 

chickpea (Cicer arietinum) be included 

on the list in § 174.27(a)(1) based on 

EPA consultations with chickpea 

experts. These consultations indicate 

that chickpea meets the three conditions 

outlined above by the SAP: It does not 

have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make chickpea weedy 

or invasive. All three experts contacted 

by EPA indicated agreement with these 

statements. For example, one expert 

stated that ‘‘there is no chance that 

chickpea would become feral with or 

without virus resistance. The 

susceptibility of the seeds to rotting 

without seed treatment would prevent 

any spread to non-crop areas. Resistance 

to viruses would not affect this 

outcome’’ (Ref. 42). EPA therefore 

believes that chickpea meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

j. Citrus. EPA proposes that citrus 

(Citrus spp.) be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with citrus experts. These 

consultations indicate that citrus meets 

the three conditions outlined above by 

the SAP. One, it does not have wild or 

weedy relatives in the United States 

with which it can form viable hybrids 

in nature. One expert mentioned that 

citrus can hybridize with other Citrus 

species and certain other closely related 

species in the sub-family Aurantioidea. 

However, this expert also noted that it 

was unlikely to hybridize naturally with 

any of these species that are found in 

the United States because they are not 

closely related and ‘‘would only be in 

the tertiary genepool for citrus’’ (Ref. 

42). Another expert pointed out that 

Rangpur lime is sometimes mentioned 

as native to Florida, but he did not think 

this was true; as far as he knew, there 

are no wild or weedy relatives of citrus 

found in the United States. Second, 

these experts agreed that citrus is not 

currently weedy or invasive in the 

United States. One expert mentioned 

that there are ‘‘small feral populations of 

citrus found in Florida, mostly on the 

borders of the Everglades area and in 

some old forests.... However, these 

populations have not expanded their 

range. I know of no weed management 

efforts’’ (Ref. 42). Third, these experts 

agreed that it is unlikely that acquisition 

of virus resistance would make citrus 

weedy or invasive. For example, one 

expert stated that ‘‘citrus is simply not 

an aggressive grower with or without a 

virus’’ (Ref. 42). EPA therefore believes 

that Citrus species meet the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

k. Coffee. EPA proposes that coffee 

(Coffea arabica and Coffea canephora) 

be included on the list in § 174.27(a)(1) 

based on EPA consultations with coffee 

experts. These consultations indicate 

that both species of coffee meet the 

three conditions outlined above by the 

SAP: They do not have wild or weedy 

relatives in the United States with 

which they can form viable hybrids in 

nature, they are not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make coffee 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘Coffee plantations that 

are abandoned usually decay and are 

not overtaken by coffee plants. The crop 

needs maintenance to grow properly. It 

is not a weedy species’’ (Ref. 42). EPA 

therefore believes that coffee meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

l. Corn. EPA proposes that corn 

(maize; Zea mays) be included on the 

list in § 174.27(a)(1) based on EPA’s 

extensive experience regulating PIPs in 

corn (Ref. 44), literature that is available 

on corn biology, the OECD Consensus 

Document on the Biology of Zea mays 

subsp. mays (Maize) (Ref. 45), and EPA 

consultations with corn experts (Ref. 

42). OECD consensus documents are 

written by national experts who freely 

consult with breeders, agronomists, and 

ecologists who are specialists in the 

field. Each document must be reviewed 

and approved by experts in the 30 

OECD member countries, and often by 

experts from non-OECD member 

countries. This body of information 

indicates that corn is low risk with 

respect to concerns associated with 

weediness. 

EPA’s 2001 risk assessment for Bt PIPs 

evaluated the potential for corn to form 

viable hybrids with wild or weedy 

relatives in the United States (Ref. 44). 

EPA’s summary conclusion was that 

while wild relatives of corn (i.e., Eastern 

Gama Grass and teosintes) may exist in 

the United States, there is no significant 

risk of gene capture and expression of 

a PIP in any of these relatives. The 

potential for pollen-directed gene flow 

from corn to Eastern Gama Grass is 

extremely remote. This is evidenced by 

the difficulty with which Tripsacum 

dactyloides x Zea mays hybrids are 

produced in structured breeding 

programs. Additionally, the genus does 

not represent any species considered as 

serious or pernicious weeds in the 

United States or its territories. Any 

introgression of genes into this species 

as a result of cross fertilization with 

genetically modified corn is not 

expected to result in a species that is 

weedy or difficult to control. In many 

instances where hybridization has been 

directed between these two species, the 

resultant genome is lacking in most or 

all of the corn chromosomal 

complement in subsequent generations. 

Many of the Zea species loosely referred 

to as ‘‘teosintes’’ will produce viable 

offspring when crossed with Zea mays 

ssp. mays. None of these plants are 

known to harbor weedy characteristics, 

and none of the native teosinte species, 

subspecies, or races are considered to be 

aggressive weeds in their native or 

introduced habitats. In fact, many are on 

the brink of extinction where they are 

indigenous and will be lost without 

human intervention (i.e., conservation 

measures). Two of the three experts EPA 

consulted indicated that corn will not 

form viable hybrids with any wild or 

weedy relatives in the United States. 


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The third indicated that hybrids could 

be formed with teosintes, but that a 

hybrid ‘‘would lose its seed dispersal 

ability, so would have highly 

diminished ability to propagate in the 

wild. In regions where teosinte is a 

weed (mostly in Mexico), the teosintes 

have been naturally selected to have 

‘gametophyte factors’ (e.g., Ga1-s, Tcb1), 

that essentially block corn pollen from 

fertilizing teosinte’’ (Ref. 42). 

Further, the body of information and 

the experts that EPA consulted on corn 

indicate that it is not currently weedy or 

invasive in the United States. None of 

the landraces or cultivated lines of Zea 

mays are considered to have weedy 

potential, and all are generally 

considered to be incapable of survival in 

the wild as a result of breeding practices 

(i.e., selection) during domestication of 

the crop. According to the OECD 

consensus document, ‘‘[m]aize has lost 

the ability to survive in the wild due to 

its long process of domestication, and 

needs human intervention to 

disseminate its seed. Although corn 

from the previous crop year can 

overwinter and germinate the following 

year, it cannot persist as a weed’’ (Ref. 

45). One expert EPA consulted stated, 

‘‘Maize does not become feral or spread 

easily into non-crop areas in the United 

States or its territories. During its 

domestication many centuries ago, 

maize lost many of the attributes 

necessary to sustain itself in nature’’

(Ref. 42). 

Finally, there is no reason to believe 

that acquisition of virus resistance 

would make corn weedy or invasive, as 

viruses are not consistently associated 

with failure of corn to show any 

evidence of being weedy or invasive. 

The experts EPA consulted agree that 

corn’s becoming weedy with acquisition 

of a PVCP-PIP is unlikely. For example, 

one expert indicated, ‘‘Domesticated 

maize has no seed dispersal mechanism. 

Humans are required to remove kernels 

from the cob (a typical cob holds 500–

1,000 kernels, which would essentially 

try to all grow in the same spot, this 

would starve the resulting plants for 

nutrients and water and result in there 

being no progeny). Maize would 

essentially die out within a year or two, 

without human intervention’’ (Ref. 42). 

EPA therefore believes that corn meets 

the conditions recommended by the 

2005 SAP for inclusion on the 

§ 174.27(a)(1) list and will present low 

risk with respect to weediness. 

m. Cowpea. EPA proposes that 

cowpea (black-eyed pea; Vigna 

unguiculata) be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with cowpea experts. 

These consultations indicate that 

cowpea meets the three conditions 

outlined above by the SAP. One, it does 

not have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature. One expert 

indicated, ‘‘the cowpea is a highly selfpollinating crop that rarely outcrosses 

with other cowpeas. I expect that it 

might be possible for cowpea to rarely 

outcross with a ‘wild’ V. unguiculata, 

but it is probably safe to assume that the 

‘wild’ cowpea genotypes don’t exist in 

the United States’’ (Ref. 42). Second, the 

experts agreed that cowpea is not 

currently weedy or invasive outside of 

agricultural fields in the United States. 

One expert said, ‘‘I am not aware of any 

instance where the cowpea has become 

feral or easily spread into non-crop 

areas in the United States. HOWEVER, 

I am aware of instances where 

cultivated cowpea varieties have 

become weed pests in cultivated areas 

in the United States where OTHER 

CROPS are grown. For example, cowpea 

varieties with hard seeds can be a weed 

problem in soybean crops. The hard 

cowpea seeds over-winter in the soil 

and can produce plants in subsequent 

years; these cowpea plants often can’t be 

easily killed by soybean herbicides 

(closely related plant) and the seeds are 

often so close in size to soybean seeds 

that [they] can be difficult to remove 

from the harvested soybean product’’

(Ref. 42). However, EPA considers that 

the key consideration is the plant’s 

behavior in natural settings, including 

semi-managed habitat surrounding 

agricultural fields, as opposed to its 

behavior within the fields themselves. 

Third, these experts agreed that it is 

unlikely that acquisition of virus 

resistance would make cowpea weedy 

or invasive. For example, one expert 

stated ‘‘I am not aware of any virus 

problem in cowpea, if resolved via 

transgenic means, would result in the 

crop becoming feral’’ (Ref. 42). EPA 

therefore believes that cowpea meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

n. Cucumber. EPA proposes that 

cucumber (Cucumis sativus) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

cucumber experts. These consultations 

indicate that cucumber meets the three 

conditions outlined above by the SAP: 

It does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make cucumber weedy 

or invasive. The experts contacted by 

EPA indicated agreement with these 

statements. For example, one expert 

stated that ‘‘cucumber could not become 

feral due to acquired transgenic virus 

resistance. The failure for [cucumber] to 

survive without human intervention is 

not due to disease attack, but rather due 

to [its] ability to compete with native 

plants and weeds, and to withstand the 

stresses they are exposed to outside of 

cultivation, particularly drought’’ (Ref. 

42). EPA therefore believes that 

cucumber meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

o. Gerbera. EPA proposes that gerbera 

(Gerbera spp.) be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with gerbera experts. Two 

experts indicated that there are no wild 

or weedy relatives in the United States 

with which gerbera can form viable 

hybrids in nature. A third said, 

‘‘Gerbera jamesonii Bolus ex Adlam has 

been recorded as naturalized in Florida. 

However, it is most likely Gerbera 

hybrida (Gerbera jamesonii x G. 

viridiflora Schultz-Bip) which is the 

designation for the commercially 

available Gerberas’’ (Ref. 42). Regarding 

the ferality of gerbera species, two 

experts believed feral populations were 

not known to occur, while a third noted, 

‘‘Although G. jamesonii (or G. hybrida) 

is attributed to Florida, it is most likely 

a low risk for forming feral populations’’

(Ref. 42). All three experts believed it 

unlikely that acquired virus resistance 

could lead to gerbera becoming feral or 

easily spreading into non-crop areas. 

One expert said, ‘‘Gerbera, in general, is 

a short-lived perennial in the United 

States. It suffers from a number of fungal 

and bacteria pathogens. A transgenic 

virus-resistant Gerbera offers little in 

terms of [increased] fitness and 

increased invasive potential’’ (Ref. 42). 

p. Gladiolus. EPA proposes that 

gladiolus (Gladiolus spp.) be included 

on the list in § 174.27(a)(1) based on 

EPA consultations with gladiolus 

experts. These consultations indicate 

that gladiolus meets the three 

conditions outlined above by the SAP: 

It does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make gladiolus weedy 

or invasive. The experts contacted by 

EPA indicated agreement with these 

statements. For example, one expert 

said, ‘‘No gladiolus species or hybrid 

has ever been documented as having 

successfully naturalized in the United 


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States. Virus resistance is not likely to 

make this any more likely’’ (Ref. 42). 

EPA therefore believes that gladiolus 

meets the conditions recommended by 

the 2005 SAP for inclusion on the list 

and will present low risk with respect 

to weediness. 

q. Lentil. EPA proposes that lentil 

(Lens culinaris) be included on the list 

in § 174.27(a)(1) based on EPA 

consultations with lentil experts. 

Although lentil was not on the list of 

plants recommended by the 2004 SAP, 

several experts consulted about other 

crops mentioned that lentil also 

appeared to meet the criteria that EPA 

was investigating. Consultations about 

lentil indicate that it meets the three 

conditions outlined above by the SAP: 

It does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make lentil weedy or 

invasive. The experts contacted by EPA 

indicated agreement with these 

statements. For example, one expert 

stated, ‘‘Lentil could not possibly 

survive in the wild on its own. [Lentils 

are] rather delicate plants, small in 

stature and very weak in competition for 

space or water. It needs great care from 

grower [sic] to produce seeds in 

cultivation. Its seed could not possibly 

survive in the wild due to rotting by 

soil-born microorganisms. Resistance to 

one or more viruses will not increase 

the survivability of lentil seeds in the 

wild’’ (Ref. 42). EPA therefore believes 

that lentil meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

r. Mango. EPA proposes that mango 

(Mangifera indica) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with mango experts. 

These consultations indicate that mango 

meets the three conditions outlined 

above by the SAP: It does not have wild 

or weedy relatives in the United States 

with which it can form viable hybrids 

in nature, it is not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make mango 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘spread of mango seed by 

humans or animals into non-crop areas 

is rare and suitable environments are 

few. Transgenic resistance should not 

affect the likelihood of spread. Viral 

susceptibility is not an important factor 

limiting the plant’s ability to become 

feral’’ (Ref. 42). EPA therefore believes 

that mango meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

s. Orchids. EPA proposes that all 

genera of orchids in the family 

Orchidaceae be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with orchid experts. 

These consultations indicate that 

orchids meet the three conditions 

outlined above by the SAP: They do not 

have wild or weedy relatives in the 

United States with which they can form 

viable hybrids in nature, they are not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make orchids weedy 

or invasive. All three experts contacted 

by EPA indicated agreement with these 

statements. For example, one expert 

stated, ‘‘Species within these genera 

have specific insect pollinators and 

those insects are unlikely [to] be present 

for pollination in United States. In 

addition, species within these genera 

are very difficult to grow from seed 

without human intervention, requiring a 

symbiotic relationship with a specific 

fungal species. Acquiring transgenic 

resistance to one or more viruses would 

not affect pollination or seed 

germination’’ (Ref. 42). EPA therefore 

believes that species in the orchid 

family meet the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

t. Papaya. EPA proposes that papaya 

(Carica papaya) be included on the list 

in § 174.27(a)(1) based on EPA 

consultations with papaya experts. 

These consultations indicate that 

papaya meets the three conditions 

outlined above by the SAP. First, it does 

not have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature. Although 

Carica papaya has been successfully 

crossed with Vasconellea species using 

laboratory-based embryo rescue 

techniques, such hybrids do not form in 

nature (Ref. 42). Second, although all 

three breeding experts agreed that 

papaya is known to establish outside of 

agricultural areas through human- and 

animal-mediated seed dispersal, the 

species is not considered to be weedy or 

invasive. For example, one expert 

stated, ‘‘I have observed small feral 

[papaya] populations in Guam, Hawaii 

and Puerto Rico... in areas close to 

human dwellings and activities.... The 

feral papayas are not weedy and are 

nonaggressive, they can easily be 

removed by cutting down.’’ Further, as 

stated in USDA-APHIS’ response to a 

petition for determination of 

nonregulated status for transgenic virusresistant papaya, ‘‘Papaya is not listed 

as a weed in the Federal Noxious Weed 

Act (7 U.S.C. 2801–2813) and is not 

reported by the Weed Society of 

America to be a common or troublesome 

weed anywhere in the United States 

(Bridges and Bauman, 1992; Holm et al. 

1979; Muenscher, 1980)’’ (Ref. 46). 

Third, two of three experts indicate 

there is no reason to believe that 

acquisition of virus resistance would 

make papaya weedy or invasive. The 

third expert said that it was ‘‘[v]ery 

likely’’ papaya would become feral or 

easily spread into non-crop areas if it 

acquired transgenic resistance to one or 

more viruses because ‘‘[a]necdotal and 

informal reports at papaya conferences 

gave evidence that the virus resistance 

transgene was found in feral 

populations’’ (Ref. 42). However, this 

comment seems to reflect the fact, as 

noted above, that papaya does 

occasionally form feral populations in 

spite of not being weedy or aggressive, 

and this characteristic would be 

expected whether the papaya is 

transgenic or not. In his comments to 

EPA, another expert concludes by 

saying that territorial records show 

papaya was not a weed in Hawaii prior 

to the discovery of papaya viruses in the 

1940s. If papaya was not considered a 

weed prior to exposure to viruses, then 

there is no reason to believe that a virus 

resistant papaya would become a weed. 

Another expert corroborates this 

conclusion by stating, ‘‘I see no 

competitive advantage of [virusresistant] transgenic papayas over 

nontransgenic papayas.... Papaya 

requires high levels of human inputs to 

thrive or survive, including fertilizers, 

chemicals and care’’ (Ref. 42). EPA 

therefore believes that papaya meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

u. Pea. EPA proposes that pea (Pisum 

sativum) be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with pea experts. These 

consultations indicate that pea meets 

the three conditions outlined above by 

the SAP: It does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature, it is not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make pea 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘pea is not likely to 

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crop areas due to acquired resistance to 

one or more viruses. Acquisition of 

transgenic viral resistance would not 

provide any adaptive advantage for 

survival of the transgenic crop plants. 

Peas have been produced in the US for 

more than 75 years with infrequent viral 

epidemics (5–9 year cycles) and no feral 

populations of pea have been recorded; 

therefore environmental and cultural 

conditions are the more likely agent 

preventing establishment of feral 

populations’’ (Ref. 42). EPA therefore 

believes that pea meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

v. Peanut. EPA proposes that peanut 

(Arachis hypogaea) be included on the 

list in § 174.27(a)(1) based on EPA 

consultations with peanut experts. 

These consultations indicate that peanut 

meets the three conditions outlined 

above by the SAP: It does not have wild 

or weedy relatives in the United States 

with which it can form viable hybrids 

in nature, it is not currently weedy or 

invasive in the United States, and there 

is no reason to believe that acquisition 

of virus resistance would make peanut 

weedy or invasive. All three experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘virus pressure is not the 

limiting factor. Even without virus 

pressure peanut (Arachis hypogaea) are 

not able to become feral or easily spread 

into non-crop areas. Peanut are not able 

to sustain long term natural populations 

without cultivation by man’’ (Ref. 42). 

EPA therefore believes that peanut 

meets the conditions recommended by 

the 2005 SAP for inclusion on the list 

and will present low risk with respect 

to weediness. 

w. Pineapple. EPA proposes that 

pineapple (Ananas comosus) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

pineapple experts. These consultations 

indicate that pineapple meets the three 

conditions outlined above by the SAP. 

One, it does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature. One expert indicated, ‘‘The 

taxonomy of the genus Ananas was 

recently critically reviewed and revised 

(Chan et al., 2003) and all of the wild 

relatives of pineapple are classified in 

the same genus and species as the 

cultivated pineapple but are different 

botanical varieties. These are Ananas 

comosus var. ananassoides and A. 

comosus var. parguazensis (Chan et al., 

2003). If these wild relatives are found 

in the United States and its territories 

they would be in cultivated gardens or 

in pots. There are no reports that A. 

comosus var comosus or its wild 

relatives survive naturally in the wild or 

pose a potential threat as weed species. 

If natural crosses between Ananas 

species occur in nature, it is highly 

unlikely that seed produced from them 

would survive to produce a mature 

plant’’ (Refs. 42 and 47). Second, the 

experts agreed that pineapple is not 

currently weedy or invasive in the 

United States. Third, these experts 

agreed that it is unlikely that acquisition 

of virus resistance would make 

pineapple weedy or invasive. For 

example, one expert stated, ‘‘Assuming 

transgenic plants were resistant to all 

known pests, pineapple still cannot 

compete with weeds, which quickly 

overtop slower growing pineapple 

plants. Pineapple lacks any natural 

mechanism for vegetative propagation 

and does not propagate naturally by 

seeds because seedlings are delicate and 

require special care to survive to 

maturity’’ (Ref. 42). EPA therefore 

believes that pineapple meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

x. Potato. EPA proposes that potato 

(Solanum tuberosum) be included on 

the list in § 174.27(a)(1) based on the 

Agency’s experience regulating PIPs in 

potato (Ref. 44), literature that is 

available on potato biology, the OECD 

Consensus Document on the Biology of 

Solanum tuberosum subsp. tuberosum 

(Potato) (Ref. 48), and EPA consultations 

with potato experts (Ref. 42). This body 

of information indicates that potato is 

low risk with respect to concerns 

associated with weediness. 

EPA’s 2001 risk assessment for Bt 

PIPs evaluated the potential for potato 

to form viable hybrids with wild or 

weedy relatives in the United States 

(Ref. 44). EPA’s conclusion was that 

there is no foreseeable risk of gene 

capture and PIP expression in wild 

relatives of Solanum tuberosum in the 

United States. Successful gene 

introgression into tuber-bearing 

Solanum species is virtually excluded 

due to constraints of geographical 

isolation and other biological barriers to 

natural hybridization (Ref. 49). These 

barriers include incompatible (unequal) 

endosperm balance numbers that lead to 

endosperm failure and embryo abortion, 

multiple ploidy levels, and 

incompatibility mechanisms that do not 

express reciprocal genes to allow 

fertilization to proceed. No natural 

hybrids have been observed between 

these species and cultivated potatoes in 

the United States. 

The body of information EPA 

consulted on potato also indicates that 

the crop is not currently weedy or 

invasive in the United States. According 

to the OECD consensus document, 

‘‘[o]utside the field, potato seedlings 

will have difficulty establishing 

themselves as they cannot compete with 

other plants. Love et al., 1994 report that 

these seedlings are limited to cultivated 

areas for reasons of competition and 

adaptation. Potato tubers can be spread 

during transportation and use, but 

generally these plants will not be 

established for a long time due to 

unfavourable environmental conditions. 

In general, the potato is not known as 

a coloniser of unmanaged ecosystems’’

(Ref. 48). One expert EPA consulted 

indicated potato ‘‘is a rare weed in 

potato plots but it never becomes feral 

in the United States’’ (Ref. 42). 

Finally, there is no reason to believe 

that acquisition of virus resistance 

would make potato weedy or invasive, 

as viruses are not consistently 

associated with failure of potato to show 

any evidence of being weedy or 

invasive. The experts that EPA 

consulted agree that it is not very likely 

that potato would become feral or easily 

spread into non-crop areas if it acquired 

transgenic virus resistance. For 

example, one expert consulted indicated 

that ‘‘[t]he basis of poor survival of 

cultivars in natural habitats is not due 

to virus susceptibility’’ (Ref. 42). EPA 

therefore believes that potato meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

y. Soybean. EPA proposes that 

soybean (Glycine max) be included on 

the list in § 174.27(a)(1) based on 

literature that is available on soybean 

biology, the OECD Consensus Document 

on the Biology of Glycine max (L.) Merr. 

(Soybean) (Ref. 50), and EPA 

consultations with soybean experts. 

This body of information indicates that 

soybean meets the three conditions 

outlined above by the SAP: It does not 

have wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make soybean weedy 

or invasive, as viruses are not 

consistently associated with failure of 

soybean to show any evidence of being 

weedy or invasive. All four experts 

contacted by EPA indicated agreement 

with these statements. For example, one 

expert stated, ‘‘Acquiring transgenic 

virus resistance will not change the 

ability of soybean to become feral since 

it will still be a domesticated species 

and does not have the attributes to 


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survive without human intervention. 

Virus diseases in the U.S. do not 

generally cause major yield loses [sic] 

and resistance to some viruses is very 

common in soybean. Transgenic virus 

resistance will not substantially change 

how the soybean interacts with most 

environments’’ (Ref. 42). According to 

the OECD consensus document, ‘‘[t]he 

soybean plant is not weedy in character. 

In North America, Glycine max is not 

found outside of cultivation. In 

managed ecosystems, soybean does not 

effectively compete with other 

cultivated plants or primary colonizers’’

(Ref. 50). EPA therefore believes that 

soybean meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

z. Starfruit. EPA proposes that 

starfruit (Averrhoa carambola) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

starfruit experts. These consultations 

indicate that starfruit meets the three 

conditions outlined above by the SAP. 

One, it does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature. One expert mentioned that 

starfruit can hybridize with wild 

Averrhoa carambola, but another expert 

indicated that researchers have 

concluded wild starfruit trees can no 

longer be found in the United States 

(Ref. 42). Second, these experts agreed 

that starfruit is not currently weedy or 

invasive in the United States. Third, 

these experts agreed that it is unlikely 

that acquisition of virus resistance 

would make starfruit weedy or invasive. 

For example, one expert stated, ‘‘It is 

highly unlikely that starfruit with 

acquired transgenic resistance would 

spread to non-crop areas because... seed 

recalcitrance in starfruit... results in a 

loss of viability shortly after harvest’’

(Ref. 42). EPA therefore believes that 

starfruit meets the conditions 

recommended by the 2005 SAP for 

inclusion on the list and will present 

low risk with respect to weediness. 

aa. Sugarcane. EPA proposes that 

sugarcane (Saccharum officinarum) be 

included on the list in § 174.27(a)(1) 

based on EPA consultations with 

sugarcane experts. These consultations 

indicate that sugarcane meets the three 

conditions outlined above by the SAP. 

One, it does not have wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature. According to one expert, 

‘‘Although in theory it should happen in 

more tropical regions of the world, 

hybrid seedlings among commercial or 

wild relatives are not observed. Breeders 

routinely generate hybrids among 

commercial sugarcane (derived from 

interspecific hybrids of Saccarhum [sic] 

officinarum and S. sponteneum), and 

among commercial and wild relatives 

(S. spontaneum mostly) under 

controlled conditions of heating and 

photoperiod control. The resulting 

progeny are quite weak and must be 

husbanded under greenhouse-type 

conditions prior to planting in the field’’

(Ref. 42). Second, these experts agreed 

that sugarcane is not currently weedy or 

invasive in the United States. One 

expert stated, ‘‘Commercial sugarcane is 

clonally propagated. Occasionally some 

of the harvested cane may be lost from 

the trucks or wagons while in transport 

from the field to the processing factory. 

If the cane has not been burned prior to 

harvest, volunteer plants occasionally 

grow along the transport route. This 

cane is not sexually reproducing, nor is 

it invasive in nature. Simple roadside 

mowing or natural weather conditions 

usually eliminate it’’ (Ref. 42). Third, 

these experts agreed that it is unlikely 

that acquisition of virus resistance 

would make sugarcane weedy or 

invasive. For example, one expert 

stated, ‘‘commercial sugar does not 

become a feral pest under regular 

commercial production conditions. The 

majority of existing commercial 

cultivars have been bred for genetic 

resistance to various disease-causing 

sugarcane viruses. None of these 

cultivars have become feral or a pest in 

anyway [sic]’’ (Ref. 42). EPA therefore 

believes that sugarcane meets the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

bb. Tulips. EPA proposes that tulips 

(Tulipa spp.) be included on the list in 

§ 174.27(a)(1) based on EPA 

consultations with tulip experts. These 

consultations indicate that tulips meet 

the three conditions outlined above by 

the SAP. One, they do not have wild or 

weedy relatives in the United States 

with which they can form viable 

hybrids in nature. Two, they are not 

currently weedy or invasive in the 

United States, although two experts 

indicated that Tulipa sylvestris 

naturalizes in certain areas without 

being viewed as a significant problem 

because it reproduces only vegetatively. 

Three, there is no reason to believe that 

acquisition of virus resistance would 

make tulips weedy or invasive. One 

expert noted that this was ‘‘possible, but 

unlikely. Virus resistance could 

conceivably increase the vigor of the 

vegetative spread of T. sylvestris’’ (Ref. 

42). However, three other experts 

believed that this was highly unlikely to 

occur. One said, ‘‘The need for chilling 

in this genus means that it is restricted 

to temperate areas with summer-cool 

climates. Areas where it can persist are 

very limited and there is a high degree 

of browsing of this genus by vertebrates 

such as deer that make seed production 

in the wild a very rare occurrence in 

nature in the U.S.’’ (Ref. 42). EPA 

therefore believes that tulips meet the 

conditions recommended by the 2005 

SAP for inclusion on the list and will 

present low risk with respect to 

weediness. 

ii. Adding plants to the categorical 

exemption criterion in § 174.27(a)(1). As 

the Agency gains additional experience, 

it may propose to add crops to the list. 

In addition, any person may petition the 

Agency to add particular crops to the 

list. EPA would evaluate any potential 

candidates against the same 

considerations used in this rulemaking 

to develop the list in § 174.27(a)(1) 

discussed above. Consequently, for a 

petition to be successful, it should 

contain sufficient data or other 

information to allow EPA to perform 

such an analysis, e.g., published 

information or a consensus opinion 

among experts in the particular crop 

that addresses the questions EPA posed 

in its expert consultations (discussed in 

Unit III.C.2.i.). Petitioners are welcome 

to consult with EPA prior to preparing 

a submission to discuss the information 

that would be required. EPA would 

consult with USDA in evaluating 

petitions for adding plants to 

§ 174.27(a)(1). 

Any subsequent addition of crops to 

the list in § 174.27(a)(1), either through 

the Agency’s own initiative or in 

response to a petition from the public, 

may only occur through rulemaking. 

Under FIFRA section 25, rulemaking 

involves several steps, including 

reviews by the SAP and USDA. In 

general, EPA would seek to expedite the 

process and proceed through direct final 

rulemaking where feasible. Under such 

a process, in cases where EPA believes 

that the proposal will not raise 

scientifically complicated issues, EPA 

would simultaneously issue a final rule 

and a proposal. If no adverse comments 

were received, the final rule would go 

into effect and EPA would withdraw the 

proposed rule. In the event of adverse 

comment, EPA would withdraw the 

final rule and would proceed to issue a 

final rule that addressed the public 

comments received on the proposal. In 

addition, as part of this current 

rulemaking, because EPA’s analysis to 

determine whether to add a crop to the 

list would be consistent with the criteria 

provided by the SAP, the Agency would 

request that the SAP generally waive its 


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review of subsequent rules seeking to 

add further crops to the list in 

§ 174.27(a)(1) unless EPA subsequently 

determines that a particular rule raised 

novel or particularly complex scientific 

issues. 

iii. Proposed exemption criterion 

conditional on Agency determination in 

§ 174.27(a)(2). EPA recognizes that 

many PVCP-PIP/plant combinations 

would reasonably be expected to pose 

low risk with respect to weediness even 

though the crop plant containing the 

PVCP-PIP is not on the Agency’s 

proposed list in § 174.27(a)(1). EPA has 

not conducted an exhaustive survey of 

all crop plants to evaluate them for 

inclusion on this list and therefore 

recognizes that additional plants may 

meet the conditions that were used to 

compile this list of plants. Therefore, in 

addition to the categorical exemption 

criterion, EPA also believes that a 

criterion conditional on Agency 

determination could be developed that 

would identify plants that are low risk 

with respect to weediness. 

EPA is considering four options for 

such a conditional exemption criterion 

under which PVCP-PIP/plant 

combinations that fail to meet 

§ 174.27(a)(1) could still meet 

§ 174.27(a) under § 174.27(a)(2), subject 

to an Agency review. Each of the 

options reflects a somewhat different 

approach to implementing the 

recommendations of the 2005 SAP (Ref. 

11). EPA does not currently have a 

preferred approach and presents several 

options to promote full consideration of 

the issues, although option 1 is 

presented in the regulatory text so the 

public could see how § 174.27(a)(2) 

might fit into the overall framework of 

the exemption. 

a. Option 1. The first option for 

§ 174.27(a)(2) provides the strictest 

interpretation of the 2005 SAP advice. 

Under this option, a PVCP-PIP would 

meet § 174.27(a) under § 174.27(a)(2) if 

the Agency determines after review that 

the plant containing the PIP meets all of 

the following: 

(i) Has no wild or weedy relatives in the 

United States with which it can form viable 

hybrids in nature. 

(ii) Is not a weedy or invasive species 

outside of agricultural fields in the United 

States. 

(iii) Is unlikely to establish weedy or 

invasive populations outside of agricultural 

fields in the United States even if the plant 

contains a PVCP-PIP. 

EPA would expect exemption 

submissions to document that the plant 

meets these conditions in the opinion of 

agronomists, breeders, ecologists, and 

other experts working with the specific 

taxa in question or based on data. When 

these conditions are met, the likelihood 

that a PVCP-PIP could cause increased 

weediness of any plant would be very 

small, as discussed in the following 

paragraphs. 

If the plant containing the PVCP-PIP 

has no wild or weedy relatives in the 

United States with which it can form 

viable hybrids in nature and thus would 

meet the criterion in § 174.27(a)(2)(i) 

under option 1, it would not be possible 

for the PVCP-PIP to inadvertently be 

transferred to any wild or weedy 

relatives, e.g., through pollen flow. 

Whether the recipient plant ‘‘can 

produce viable hybrids in nature’’ is a 

critical attribute that would definitively 

determine the potential for introgression 

of the PVCP-PIP into a native or 

naturalized plant population. Although 

hybrids must be able to reproduce 

themselves in order for introgression to 

occur, the production of ‘‘viable’’

hybrids (i.e., those that are able to grow) 

may be described more clearly in a 

regulatory standard than examining the 

reproductive potential of any hybrids. In 

many cases, reproductive potential of 

hybrids has not been fully investigated. 

Given that reduced fertility in F1 cropwild hybrids is frequently restored to 

normal in subsequent generations (Ref. 

37), measurement of hybrid fertility 

involves consideration of several 

generations. In addition, viability is a 

more reliable standard because even 

very low rates of gene transfer could 

lead to introgression (Ref. 51), 

suggesting that any degree of hybrid 

fertility could indicate the potential for 

introgression to occur. As noted by the 

2005 SAP, ‘‘it is known that favorable 

alleles (including, perhaps, a PVCP-PIP) 

can pass easily from one species to 

another through hybrid zones, even 

when the hybrids have very low fitness 

(Barton 1986)’’ (Refs. 11 and 52). The 

Agency recognizes that introgression of 

a trait such as virus resistance into 

natural plant populations does not 

automatically confer a competitive 

advantage to the recipient population. 

However, at this time, there is little 

information available to predict 

categorically whether acquisition of 

such a trait might affect the 

competitiveness of a specific plant 

population, and the available 

information does not allow the Agency 

to make this determination a priori. The 

ability to produce viable hybrids is 

relatively easy to evaluate, resulting in 

a clear criterion that ensures an effective 

limitation on the potential for 

introgression. Such language also 

clarifies that the relevant question is 

whether the hybrid can be produced ‘‘in 

nature.’’ The fact that plants could be 

crossed in the laboratory or greenhouse 

is not necessarily indicative of a plant’s 

true reproductive potential. The 

Agency’s focus is whether a viable 

hybrid could be produced under normal 

growing conditions in the field or in 

nature, rather than under controlled 

experimental conditions that might have 

little relevance to behavior in the 

environment. 

If the plant containing the PVCP-PIP 

is not a weedy or invasive species 

outside of agricultural fields in the 

United States and thus would meet the 

criterion in § 174.27(a)(2)(ii) under 

option 1, established and persistent feral 

populations of the crop presenting 

difficult management issues in natural 

or semi-managed ecosystems would be 

unlikely. Thus, transfer of the PVCP-PIP 

from the crop to a feral population 

would be unlikely to exacerbate what 

could already be a difficult problem by 

inadvertently increasing the 

population’s weediness potential. EPA 

proposes inclusion of the term ‘‘outside 

of agricultural fields’’ to emphasize that 

the key consideration is the plant’s 

behavior in natural settings, including 

semi-managed habitat surrounding 

agricultural fields as opposed to its 

behavior within the fields themselves. 

EPA recognizes that most crops within 

agricultural fields form volunteer 

populations, where propagules of the 

crop from the previous rotation grow in 

the subsequent crop rotation. The 

Agency believes the language ‘‘outside 

of agricultural fields’’ appropriately 

excludes this situation from 

consideration. 

If the plant containing the PVCP-PIP 

is unlikely to establish weedy or 

invasive populations outside of 

agricultural fields in the United States 

even if the plant contains a PVCP-PIP 

and thus would meet the criterion in 

§ 174.27(a)(2)(iii) under option 1, an 

additional level of assurance would be 

provided that the crop plant would not 

present weediness concerns through 

acquisition of a PVCP-PIP. EPA believes 

that this condition could in general be 

met based on the opinion of experts on 

the particular crop. Experts may judge, 

for example, that acquisition of virus 

resistance is unlikely to change the 

weedy or invasive characteristics of the 

plant if the crop does not appear to be 

weedy or invasive when virus infection 

is known to be absent from a particular 

area or over a particular period of time. 

Available empirical data could be used 

in the determination or may be gathered 

if expert opinion cannot resolve the 

question. 

EPA proposes to define the term 

‘‘weedy species’’ used in 

§ 174.27(a)(2)(ii) to mean ‘‘a species that 


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is an aggressive competitor in natural 

ecosystems.’’ EPA intends to use the 

term ‘‘invasive species’’ consistent with 

the definition in Executive Order 13112, 

meaning an alien species whose 

introduction causes or is likely to cause 

economic or environmental harm or 

harm to human health. An alien species 

means, with respect to a particular 

ecosystem, any species, including its 

seeds, eggs, spores, or other biological 

material capable of propagating that 

species, that is not native to that 

ecosystem. EPA uses the phrase ‘‘weedy 

or invasive populations’’ in 

§ 174.27(a)(2)(iii) consistent with these 

definitions. 

EPA notes that the criterion in 

§ 174.27(a)(2)(i) under option 1 does not 

necessarily strictly hold for every crop 

that appears on the list in proposed 

§ 174.27(a)(1). In some cases, EPA was 

able to make a low risk determination 

for a particular crop, e.g., corn, in spite 

of the possible presence of wild or 

weedy relatives in the United States 

with which the plant may in rare cases 

form viable hybrids in nature. EPA has 

presented the basis for such conclusions 

in this proposed rule, and the public 

can clearly understand why the crops in 

§ 174.27(a)(1) meet the Agency’s low 

risk standard with respect to weediness 

concerns. Given that several crops for 

which EPA has made a low risk 

determination and proposes to include 

in § 174.27(a)(1) would not meet 

§ 174.27(a)(2) as proposed under option 

1, EPA believes that option 1 may be too 

narrow. Accordingly, EPA is 

considering other options for 

§ 174.27(a)(2) that are based on a less 

literal interpretation of the SAP’s 

recommendations but which the Agency 

believes are nevertheless consistent 

with the SAP’s intent. 

b. Option 2. The second option EPA 

is considering is that a PVCP-PIP would 

meet the criterion in § 174.27(a)(2)(i) if 

‘‘the plant containing the PIP has no 

wild or weedy relatives in the United 

States with which it can form viable, 

fertile hybrids in nature, or if fertile, the 

resulting hybrid cannot establish 

populations in the environment.’’ EPA 

is considering this option because most 

crops are able to form viable hybrids 

with a wild or weedy relative in some 

part of the United States. However, 

some viable, fertile hybrids may 

nevertheless present low risk with 

respect to concerns associated with 

weediness, e.g., if the hybrids are weak 

and lack the ability to establish. On the 

other hand, fertility and the potential to 

establish are more difficult 

characteristics to evaluate than viability 

because many more variables affect the 

determination, suggesting that it might 

be more appropriate in these cases for 

the Agency to require that data be 

collected for a period of time after 

commercial deployment that could 

confirm the Agency’s original analysis. 

However, while such conditions may be 

readily placed on a PVCP-PIP 

registration, they could not be placed on 

an exempt PVCP-PIP. In addition, 

determinations under option 2 would be 

more difficult for the public to predict 

than determinations under option 1, as 

discussed in Unit III.A.2. 

c. Option 3. Under the third option 

being considered, EPA would adopt 

only the criteria in § 174.27(a)(2)(i) and 

(a)(2)(ii) as discussed above under 

option 1. The rationale for such an 

approach is that it may not be necessary 

to evaluate the criterion in 

§ 174.27(a)(2)(iii) in order to make a low 

risk determination because the issues 

are adequately addressed by the other 

two criteria. Viruses generally do not 

uniformly affect crops every season in 

every place they are planted - even 

those crops that viruses significantly 

impact such that development of a 

PVCP-PIP to combat the disease might 

be undertaken. Crops will thus have 

repeated opportunity to escape 

cultivation in seasons and in areas 

where there is no virus infestation. If 

weedy tendencies are rarely or never 

observed in any part of the crop’s range, 

it is unlikely that virus resistance affects 

the crop’s ability to escape cultivation 

and establish weedy populations. 

Unlike wild or weedy plant relatives 

that may at times be infected by viruses 

and may be negatively impacted by 

viruses in ways that are not obvious to 

untrained observers, breeders and 

farmers are intimately aware of the type 

of damage done by virus infection to 

crops and are therefore well aware when 

their fields are or are not infected. Crop 

plants have been observed under a 

diverse range of environmental 

conditions over many years. If a PVCPPIP were likely to make a crop weedy 

or invasive, such tendencies would 

likely have been observed even without 

virus resistance at some point in time 

given the level of observation crops 

generally receive due to the necessity to 

actively manage their cultivation. Such 

crops showing weedy or invasive 

tendencies would not meet the criterion 

in § 174.27(a)(2)(ii), suggesting that the 

criterion in § 174.27(a)(2)(iii) is largely 

redundant with this condition. 

EPA notes that option 3 is likely to be 

equally as narrow as options 1 and 2. 

The advantage of the option would be 

a simplification of the issues that a 

PVCP-PIP developer would need to 

address as part of a submission for an 

exemption determination. 

EPA could consider factors that are 

not considered under options 1–3 but 

that would affect the potential impact of 

PVCP-PIP acquisition as part of 

evaluating a PVCP-PIP for FIFRA 

registration. For example, EPA could 

take into account the effect of virus 

infection on such species, the existence 

and impact of any natural virus 

resistance in the population, the overlap 

of the plant’s distribution with crop 

cultivation areas, and other relevant 

considerations. 

d. Option 4. The fourth option EPA is 

considering is that a PVCP-PIP would 

meet § 174.27(a)(2) if the Agency 

determines that ‘‘the PVCP-PIP is 

unlikely to significantly change the 

population size or distribution of the 

species containing the PVCP-PIP outside 

of agricultural fields or the population 

size or distribution of any wild or 

weedy species in the United States that 

could acquire the PVCP-PIP through 

gene transfer.’’ EPA is considering this 

fourth option because the Agency 

recognizes that many PVCP-PIPs 

excluded from exemption under the 

criterion in § 174.27(a)(2)(i) of options 

1–3 because of wild or weedy relatives 

in the United States may nevertheless 

present low risk. The presence of wild 

or weedy relatives relates only to 

potential exposure of the PVCP-PIP and 

does not indicate whether the PVCP-PIP 

is likely to cause any adverse effects 

even if it were to transfer to these 

relatives. EPA believes that such an 

evaluation would be consistent with the 

advice of the 2005 SAP, which noted 

that ‘‘[t]he probability that a particular 

transgene will lead to increased 

weediness depends on the phenotype 

conferred by the transgene and on the 

ecological factor(s) currently limiting 

the size or distribution of the wild 

species. In particular, if the transgene 

alters plant response to an ecological 

factor limiting population size, then 

population dynamics may be affected. 

For PVCP-PIPs, the relevant 

consideration is whether virus 

resistance (conferred by the PVCP-PIP) 

leads to changes in the size or 

distribution of wild plant species with 

the PVCP-PIP’’ (Ref. 11). 

With option 4, EPA would conduct a 

risk assessment to evaluate a clear end 

point - whether there is likely to be a 

significant change in the population size 

or distribution of the species containing 

the PVCP-PIP outside of agricultural 

fields or the population size or 

distribution of any wild or weedy 

species in the United States that could 

acquire the PVCP-PIP through gene 

transfer. However, for the vast majority 

of species, many characteristics that 

would influence this determination are 


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currently poorly understood, e.g., the 

impact of virus infection on wild plant 

populations and the likely selective 

advantage afforded by acquisition of 

virus resistance. As a result, both the 

nature of EPA’s evaluation and the type 

and extent of data that might need to be 

provided to the Agency resemble much 

more closely what would be required to 

evaluate weediness issues during a 

FIFRA registration review. In addition, 

the more the exemption determination 

process resembles a full risk assessment, 

the longer the time required for EPA to 

complete such a review. 

Although EPA would seek public 

comment on determinations that a 

PVCP-PIP met § 174.27(a)(2) according 

to the procedure for exemptions 

utilizing any Agency-determined 

criteria, Agency determinations may be 

more controversial with this option than 

with other options that have more 

clearly defined criteria. EPA believes 

that case-by-case determinations could 

be made appropriately and that the data 

requirements needed to evaluate the 

criterion under option 4 would not 

necessarily be overly burdensome. EPA 

notes that in many cases much of the 

data, if not all, needed for EPA to 

evaluate a criterion such as this fourth 

option would also be needed for a 

petition for determination of 

nonregulated status submitted to USDA. 

EPA believes that the flexibility of this 

option will make it more likely that the 

Agency would identify the largest 

number of low risk products that could 

qualify for exemption. 

For all options for proposed 

§ 174.27(a)(2), the Agency believes the 

entire United States is the relevant 

scope of inquiry because the proposed 

exemption would carry no limitations 

on where the exempted PVCP-PIP/plant 

combination could be planted and thus 

could be planted in all areas subject to 

U.S. law. FIFRA section 2(aa) defines 

‘‘State’’ as ‘‘a State, the District of 

Columbia, the Commonwealth of Puerto 

Rico, the Virgin Islands, Guam, the 

Trust Territory of the Pacific Islands, 

and American Samoa. Accordingly, the 

term ‘‘United States’’ used in this 

proposal includes all these areas, and 

EPA proposes to incorporate a 

definition of ‘‘United States’’ paralleling 

the FIFRA definition of ‘‘State’’ into the 

definitions in 40 CFR 174.3. 

As an alternative to Agency review 

pursuant to § 174.27(a)(2), a developer 

could petition EPA to add a crop to the 

list in § 174.27(a)(1). In some cases, EPA 

expects that the same data/information 

that would support a determination that 

a crop meets § 174.27(a)(2) would 

support listing the crop in 

§ 174.27(a)(1). However, because a plant 

can only be added to the list in 

§ 174.27(a)(1) through rulemaking, EPA 

expects that many developers will 

instead prefer to obtain an Agency 

determination under § 174.27(a)(2). 

However, once a plant is added to the 

list in § 174.27(a)(1), future PVCP-PIPs 

used in that plant would meet 

§ 174.27(a) without any Agency review. 

3. Historical approaches. In 1994 EPA 

proposed two different alternatives for 

exempting PVCP-PIPs from FIFRA 

requirements. The Agency prefers the 

approaches discussed in the preceding 

Subunit because they have been 

developed based on recent interactions 

with the SAP and thus represent the 

most current science. One 1994 

alternative contained exemption criteria 

directed towards addressing concerns 

associated with gene transfer to identify 

those PVCP-PIP/plant combinations 

with the lowest potential to confer 

selective advantage on wild or weedy 

plant relatives. EPA described this 

alternative exemption as follows: 

Coat proteins from plant viruses [would be 

exempt] if the genetic material necessary to 

produce a coat protein is introduced into a 

plant’s genome and the plant has at least one 

of the following characteristics: 

(1) The plant has no wild relatives in the 

United States with which it can successfully 

exchange genetic material, i.e., corn, tomato, 

potato, soybean, or any other plant species 

that EPA has determined has no sexually 

compatible wild relatives in the United 

States. 

(2) It has been demonstrated to EPA that 

the plant is incapable of successful genetic 

exchange with any existing wild relatives 

(e.g., through male sterility, self-pollination). 

(3) If the plant can successfully exchange 

genetic material with wild relatives, it has 

been empirically demonstrated to EPA that 

existing wild relatives are resistant or 

tolerant to the virus from which the coat 

protein is derived or that no selective 

pressure is exerted by the virus in natural 

populations (59 FR 60504, November 23, 

1994). 

EPA carefully reconsidered this 1994 

proposal in its deliberations for today’s 

proposed exemption and presented 

these criteria in modified form to the 

FIFRA SAP at the October 2004 and 

December 2005 meetings for 

consideration. In light of comments 

received from the FIFRA SAP and 

additional scientific information 

available since 1994, EPA no longer 

believes this alternative would 

adequately address questions associated 

with weediness in a manner that could 

be reasonably implemented. However, 

EPA still considers that it would be 

appropriate to limit the exemption 

based on the concerns outlined in the 

earlier proposal associated with 

acquisition of virus resistance through 

hybridization with a transgenic plant 

containing a PVCP-PIP. 

Although similar in intent to 

characteristic (1) of this option proposed 

in 1994, today’s proposed criterion in 

§ 174.27(a)(2)(i) under option 1 focuses 

in part on the potential to ‘‘form viable 

hybrids in nature’’ rather than simply 

‘‘exchange genetic material’’ because the 

former is a clearer standard for 

determining whether a PVCP-PIP could 

have the potential to affect a recipient 

plant population negatively. The ability 

to exchange genetic material, which is 

often demonstrated by performing hand 

crosses in the laboratory or greenhouse, 

may not indicate any relevant 

information about how the plants would 

behave in nature. Today’s proposed 

criterion in § 174.27(a)(1) also uses a 

somewhat different list of plants than 

the four in the 1994 proposal. Several 

species have been added (see Unit 

III.C.2.i.) and tomato has been removed 

from the list because of information 

acquired through expert consultation. 

(See Unit VII for a discussion of this 

information and to read EPA’s request 

for comment). When EPA presented a 

criterion similar to the first 

characteristic in the 1994 proposal to 

the 2004 SAP, they responded that ‘‘the 

Panel was of the opinion that the 

absence of a competent wild/weedy 

relative positioned in relation to the 

plant containing the PVCP-PIP was an 

appropriate condition.’’ The 2005 SAP 

also ‘‘was supportive of the Agency’s 

intent to exempt from regulation any 

PVCP-PIP crops that (1) do not have 

sexually compatible wild relatives in 

the location of intended cultivation (US 

& Territories) and (2) are not likely to 

become weedy themselves’’ (Ref. 11). 

EPA now also believes that 

characteristic (2) of the option proposed 

in 1994 may be insufficient based on the 

conclusions of the 2004 SAP and the 

National Research Council that current 

methods of bioconfinement are 

imperfect and are unlikely to adequately 

restrict gene flow (Refs. 25 and 53). The 

Agency asked the 2004 SAP whether the 

condition that ‘‘genetic exchange 

between the plant into which the PVCPPIP has been inserted and any existing 

wild or weedy relatives is substantially 

reduced by modifying the plant with a 

scientifically documented method, (e.g., 

through male sterility)’’ would be 

necessary and/or sufficient to minimize 

the potential for a PVCP-PIP to harm the 

environment through gene transfer from 

the crop plant containing the PVCP-PIP 

to wild or weedy relatives. The Panel 

‘‘accepted that tactics aiming at 

diminished gene exchange are highly 

desirable and even necessary but are not 

sufficient’’ (Ref. 25). 


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In spite of such concerns, EPA is still 

considering whether a criterion 

involving biocontainment could be 

sufficient to enable the Agency to 

determine with review that a product 

presents low risk with respect to 

concerns associated with weediness. 

The 2005 SAP concluded ‘‘that if highly 

effective biological containment and 

biological mitigation methods could be 

deployed concurrently with the PVCPPIP, then it would be possible to exempt 

crops with sexually compatible wild 

relatives. This opinion is different from 

the opinion of the October 2004 FIFRA 

SAP. The [2005] Panel concluded that 

this difference is probably due to 

advances in containment and mitigation 

strategies. For this reason, exemptions 

might be granted to any crop that 

hybridizes with a wild relative in the 

US, its possessions or territories, if the 

F1 and BC (backcross) hybrids have very 

low fitness such that it is effectively 

lethal. Additionally, an exemption 

might be possible if specific genes for 

lowering fitness are in tandem 

constructs with the PVCP-PIP gene in 

such a way that they cannot readily 

segregate from each other. The Panel did 

not determine what level of 

effectiveness would be required but, it 

was agreed that stacked strategies would 

reduce the cumulative risk, and should 

be strongly considered’’ (Ref. 11). 

Bioconfinement strategies are known 

to have a wide range of efficacy, and no 

standard level of efficacy to ensure 

environmental safety has been 

determined (Ref. 53). Additionally, 

some techniques may introduce risk 

concerns that must be evaluated, e.g., 

unintended impacts on wildlife that eat 

seeds or pollen (Ref. 25). However, 

scientific advancements may make 

bioconfinement techniques sufficiently 

reliable and safe in the future such that 

deployment with a PVCP-PIP would be 

sufficient to reach a low risk finding 

with respect to concerns associated with 

weediness (Refs. 54 and 55). Therefore, 

EPA is still considering a condition 

such as characteristic (2) proposed in 

1994 that would constitute an 

alternative way to meet § 174.27(a)(2) 

under any of the options discussed in 

this Preamble. For example, 

§ 174.27(a)(2) might read: 

The Agency determines after review that 

the plant containing the PIP: 

(i) Has no wild or weedy relatives in the 

United States with which it can form viable 

hybrids in nature or employs a highly 

effective biological containment technique. 

(ii) Is not a weedy or invasive species 

outside of agricultural fields in the United 

States or employs a highly effect 

biomitigation construct that ensures escapes 

from cultivation are too unfit to compete 

with wild-types. 

EPA believes that characteristic (3) of 

the option proposed in 1994 is sound 

conceptually. However, the Agency’s 

intent in developing this exemption has 

historically been to have criteria that 

identify low risk PVCP-PIPs such that 

the criteria could be evaluated with 

information that a developer is likely to 

have acquired in the course of 

developing the product and not require 

significant data generation. The Agency 

presented a similar criterion to the 2004 

SAP for their consideration: ‘‘all 

existing wild or weedy relatives in the 

United States with which the plant can 

produce a viable hybrid are tolerant or 

resistant to the virus from which the 

coat protein is derived.’’ The Panel 

members suggested that such a criterion 

would be difficult to implement in a 

clear and transparent exemption review 

process given that ‘‘[t]he Panel had 

particular difficulty when attempting to 

add precision to approaches that should 

be followed when sampling wild and 

weedy relatives for the occurrence of 

specific virus tolerance or resistance as 

specified by the Agency.’’

As an alternative to a criterion like 

that described by characteristic (3) in 

the 1994 proposal whose evaluation 

would necessitate collection of 

potentially significant amounts of data, 

EPA presented another option to the 

2005 SAP: ‘‘(i) the plant containing the 

PVCP-PIP is itself not a weedy or 

invasive species outside of agricultural 

fields in the United States, its 

possessions, or territories, and (ii) the 

plant containing the PVCP-PIP does not 

have relatives outside of agricultural 

fields in the United States, its 

possessions, or territories that are weedy 

or invasive species or endangered/ 

threatened species with which it can 

produce viable hybrids in nature’’ (Ref. 

11). However, the Panel concluded that 

‘‘the probability that a particular 

transgene alters the dynamics of a wild 

relative cannot be predicted by the 

current status of the wild species as 

weedy, invasive, or threatened/ 

endangered. The Panel agreed that the 

criteria proposed by the Agency would 

not correctly identify PVCP-PIPs which 

pose unacceptable environmental risks’’

(Ref. 11). EPA has therefore concluded 

that the Agency is unable at this time to 

articulate a clear criterion for exemption 

that would expand the eligible plants 

beyond those roughly described by the 

ideas in the 1994 characteristic (1) 

unless the Agency were to adopt a 

criterion whose evaluation involved 

conducting a risk assessment of the 

PVCP-PIP/plant combination such as it 

put forth in this preamble as the fourth 

option for proposed § 174.27(a)(2), i.e., 

that the PVCP-PIP is unlikely to 

significantly change the population size 

or distribution of the species containing 

the PVCP-PIP outside of agricultural 

fields or the population size or 

distribution of any wild or weedy 

species in the United States that could 

acquire the PVCP-PIP through gene 

transfer (discussed in Unit III.C.2.iii.d.). 

The other alternative proposed in 

1994 did not contain a criterion 

addressing concerns associated with 

gene flow. This option proposed a full 

categorical exemption for all PVCP-PIPs 

(59 FR 60503). This option is no longer 

the Agency’s preferred approach for a 

number of reasons. Specifically, EPA 

has received scientific advice since 

issuance of the 1994 proposal calling 

into question the Agency’s 1994 

rationale that all PVCP-PIPs meet the 

FIFRA 25(b)(2) exemption standard, 

including gene flow considerations. 

Although EPA believes that many 

PVCP-PIPs present low risk and thus 

meet the FIFRA 25(b)(2) exemption 

standard, in order to categorically 

exempt all PVCP-PIPs, the Agency must 

be able to draw this conclusion for all 

PVCP-PIPs. Advances in scientific 

understanding since 1994 suggest it may 

not be possible to support this rationale 

for all PVCP-PIPs and that certain PVCPPIPs may pose a greater level of risk 

than is characteristic of the group as a 

whole. For example, virus resistance is 

common in natural plant populations as 

evidenced by conventionally bred virus 

resistant plants that are only possible 

due to naturally existing resistance in 

crop and wild relative populations (Ref. 

20). This fact suggests that acquisition of 

virus resistance is often unlikely to 

introduce a novel trait into many plant 

populations. However, some notable 

exceptions to the ubiquity of virus 

resistance in natural plant populations 

exist including the lack of successful 

conventionally bred resistance to barley 

yellow dwarf virus in major crops and 

the lack of natural resistance in some 

wild relatives of these crops (Ref. 36). 

Such information suggests that 

acquisition of a PVCP-PIP by such wild 

relatives of these plants has the 

potential to free these wild relatives 

from what may be an important 

ecological constraint. The conclusions 

of the 2004 FIFRA SAP are consistent 

with the idea that it may not be possible 

to apply a general exemption rationale 

to all PVCP-PIPs. The report concluded 

that ‘‘...PVCP-PIPs [have] no inherent 

capacity to harm the environment.’’

However, ‘‘[i]t was recognized that 

knowledge of hybridization potential 

was sparse and of very unequal quality 

but the likelihood of serious economic 


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harm was such that some plants 

engineered to contain stress tolerant 

traits should not be released’’ (Ref. 25). 

The 2005 SAP’s conclusions discussed 

above also clearly suggest that crops 

containing a PVCP-PIP that have wild 

relatives must be carefully considered 

on a case-by-case basis (Ref. 11). 

Similarly, the 2000 National Research 

Council (NRC) report recommended that 

because of concerns associated with 

hybridization with weedy relatives, 

‘‘EPA should not categorically exempt 

viral coat proteins from regulation 

under FIFRA. Rather, EPA should adopt 

an approach, such as the agency’s 

alternative proposal..., that allows the 

agency to consider the gene transfer 

risks associated with the introduction of 

viral coat proteins to plants’’ (Ref. 10). 

D. Viral Interactions 

1. Scientific issues. In addition to 

weediness, a key issue associated with 

PVCP-PIPs is the question of whether 

they could affect the epidemiology and 

pathogenicity of plant viruses. Given the 

potential impact of virus infection, such 

changes might affect competitiveness of 

plant populations thereby altering 

ecosystem dynamics, e.g., through 

significant changes in species 

composition of populations, resource 

utilization, or herbivory. 

The genetic material of plant viruses 

may be composed of either RNA or 

DNA, although most have RNA genomes 

(Ref. 56). Although there are significant 

differences between RNA and DNA 

viruses, both are obligate parasites that 

usually move from plant to plant via 

vector-mediated transmission. Such 

transmission, in connection with other 

types of virus transmission, commonly 

leads to mixed viral infections in crops 

and other plants (Ref. 57). In natural, 

mixed infections, viral genomes from 

different strains and/or different species 

simultaneously infect the same plant 

and thus have opportunities to interact 

(e.g., through recombination, 

heterologous encapsidation, or synergy). 

In spite of many opportunities for 

interaction in nature, such events rarely 

lead to any detectable adverse outcome 

(Ref. 58). However, such in planta 

interactions have the potential to result 

in a virus that causes increased 

agricultural or other environmental 

damage. 

In transgenic plants containing PVCPPIPs, every virus infection can be 

considered in one sense to be a mixed 

infection with respect to the coat 

protein gene (Ref. 59). The key 

questions facing EPA are whether 

interactions between such introduced 

plant virus sequences and infecting 

viruses in transgenic plants may 

increase in frequency or be unlike those 

expected to occur in nature (Ref. 60). 

The Agency has written a literature 

review addressing these questions (Ref. 

60) and will briefly describe the issues 

associated with recombination, 

heterologous encapsidation, and 

synergy below. EPA provides a general 

overview of each of the processes 

separately, followed by a brief review of 

relevant field studies that investigated 

these processes. 

i. Recombination. Recombination is a 

natural process that can occur during 

replication of DNA or RNA whereby 

new combinations of genes are 

produced. Plant virus recombination 

can occur between members of the same 

virus pathotype in natural infections, 

contributing to the number of variants 

that exist within that pathotype. 

Recombination can also occur when 

different viruses coinfect the same plant 

and interact during replication to 

generate virus progeny that have genetic 

material from each of the different 

parental genomes. Although 

recombination likely occurs regularly in 

mixed viral infections, recombination 

only rarely leads to viable viruses and 

even more rarely to viruses with truly 

novel behavior and/or characteristics or 

any detectable adverse outcome. In 

order to persist in nature, a recombinant 

virus must be competitive with variants 

of the parental viruses that have already 

demonstrated success in all stages of the 

infective cycle, e.g., transmission, gene 

expression, replication, and assembly of 

new virions (Ref. 58). An analysis of 

cucumber mosaic virus (CMV) isolates 

in natural populations showed that 

viable recombinants were very rarely 

recovered in mixed infections (Ref. 61). 

Although selection in the field 

appears to act against persistence of 

new, recombinant viruses, 

recombination is thought to play a 

significant role in virus evolution, 

presumably because recombinant 

viruses are on very rare occasions able 

to outcompete existing viruses. How a 

virus with increased pathogenicity or 

altered epidemiology might conceivably 

be created through recombination was 

suggested by a laboratory experiment in 

which a pseudorecombinant strain was 

created by experimentally combining 

regions of the CMV and tomato aspermy 

virus (TAV) genomes. This artificially 

manipulated virus was found to cause 

more severe symptoms than either of the 

parental genomes, although the 

recombinant was not a fully-functional 

virus as it was not able to move beyond 

the initially infected cells (Ref. 62) and 

would therefore not be expected to 

persist in nature. Another laboratory 

experiment has shown interspecific 

recombination between CMV and TAV 

under conditions in which 

recombinants would not be expected to 

have any particular fitness advantage 

(Ref. 63). In another example, alteration 

of the host range of tobacco mosaic virus 

(TMV) occurred when a chimeric virus 

expressed the coat protein from alfalfa 

mosaic virus (AMV) instead of its own 

(Ref. 64). 

Evidence of past recombination 

having led to the creation of new RNA 

viruses has been documented in a 

number of different groups including 

bromoviruses (Ref. 65), luteoviruses 

(Ref. 66), nepoviruses (Ref. 67), and 

cucumoviruses (Ref. 68). Sequence 

analysis of viruses from the family 

Luteoviridae indicated that this family 

has evolved via both intra- and 

interfamilial recombination (Ref. 69). 

Interspecific recombination between 

two related potyviruses, soybean mosaic 

virus (SMV) and bean common mosaic 

virus (BCMV) apparently led to the 

creation of watermelon mosaic virus 

(WMV) with a broader host range than 

either SMV or BCMV (Ref. 70). Whereas 

these latter two viruses are generally 

restricted to Leguminosae, WMV has 

one of the broadest host ranges among 

the potyviruses being able to infect both 

monocots and dicots. For RNA viruses, 

evidence of recombinant viruses arising 

in recent history has not been reported, 

suggesting that recombination as a factor 

in RNA virus evolution may generally 

only be significant over a longer 

timescale. 

Recombination has also played a role 

in the evolution of new DNA viruses 

including caulimoviruses (Ref. 71) and 

geminiviruses (Refs. 72 and 73). For 

DNA viruses, geminiviruses in 

particular, several instances can also be 

cited in which relatively recent 

recombination events appear to have 

resulted in the creation of new viruses. 

For example, a recent epidemic of 

severe cassava mosaic disease in 

Uganda is thought to be due to the 

combination and/or sequential 

occurrence of several phenomena 

including recombination, 

pseudorecombination, and/or synergy 

among cassava geminiviruses (Ref. 72). 

It also appears that tomato-infecting 

begomoviruses that have emerged in the 

last 20 years around the Nile and 

Mediterranean Basins probably resulted 

from numerous recombination events 

(Ref. 74). In addition, a natural 

recombinant between tomato yellow leaf 

curl Sardinia virus and tomato yellow 

leaf curl virus was detected in southern 

Spain with a novel pathogenic 

phenotype that might provide it with 

selective advantage over the parental 

genotypes (Ref. 75). Finally, analysis of 


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a newly described Curtovirus species 

associated with disease of spinach in 

southwest Texas suggests that it may be 

the result of recombination among 

previously described Curtovirus species 

(Ref. 76). 

In addition to virus-virus 

recombination, recombination has also 

been found to occur between virus and 

plant host RNA. Sequence analysis of 

the 5’ terminal sequence of potato 

leafroll virus (PLRV) suggests that it 

arose via recombination with host 

mRNA (Ref. 77). Evidence suggests that 

such recombination events can affect 

virus virulence (for review see Ref. 78). 

Like a plant host genome, transcripts of 

viral transgenes would be available for 

recombination with infecting viruses, 

and portions of the transgene could thus 

be incorporated into the replicating 

virus. Several laboratory experiments 

have investigated the potential for 

recombination between viral transgenes 

and infecting viruses of the same 

species. These experiments show that 

recombination can occur between viral 

transgenes and both RNA viruses (Refs. 

79, 80, 81, 82, and 83) and DNA viruses 

(Refs. 84, 85, 86, and 87). However, the 

relevance to PVCP-PIPs of the latter 

experiments with DNA viruses is 

unclear because the transgenic plants 

used in the experiments actually show 

no viral resistance; attempts to develop 

transgenic DNA virus-resistant plants in 

general have had little success (Ref. 57). 

In addition, to facilitate the detection of 

recombinants, most of these 

experiments were conducted under 

conditions of high selective pressure 

favoring the recombinant, i.e., only 

recombinant viruses were viable. The 

selective pressure under normal field 

conditions would likely favor the 

parental viruses rather than a 

recombinant as parental viruses will be 

competent in all of the functions needed 

for propagation and will outnumber the 

new recombinant. 

ii. Heterologous encapsidation. 

Heterologous encapsidation occurs 

when the coat protein subunits of one 

virus surround and encapsidate the viral 

genome of a different virus. The coat 

protein, possibly in conjunction with 

other viral factors, is often essential for 

transmission and responsible for 

conferring the high degree of vector 

specificity. Therefore, a heterologously 

encapsidated viral genome may be 

transmitted by the vectors of the virus 

contributing the coat protein rather than 

the vectors of the virus contributing the 

viral genome. For many viruses, 

transmission from plant to plant occurs 

by insect vectors, and each virus tends 

to be transmitted by only one type of 

insect (Ref. 1). To the extent that vectors 

visit different groups of plants, vectors 

carrying a heterologously encapsidated 

viral genome may carry it to a plant the 

virus does not normally encounter (Ref. 

59). 

Most evidence of heterologous 

encapsidation is derived from laboratory 

or greenhouse studies. Even though 

there is a high frequency of mixed 

infections in nature, most mixed 

infections do not lead to heterologous 

encapsidation, and those virus 

interactions that do occur tend to be 

very specific rather than random 

interactions between unrelated viruses 

(Ref. 88). Only among some types of 

plant viruses is heterologous 

encapsidation regularly observed. Its 

frequency depends on the relationship 

between the viruses involved, being 

more likely to occur among closely 

related viruses (Ref. 89). An expansion 

of aphid vector specificity due to 

heterologous encapsidation was first 

observed in plants infected with two 

different isolates of barley yellow dwarf 

virus (BYDV; Ref. 90) and was later 

shown to be a general phenomenon 

among these viruses in natural 

populations of several plant species 

(Ref. 91). Heterologous encapsidation 

was also shown to occur in potyviruses. 

An isolate of zucchini yellow mosaic 

virus (ZYMV) that is normally nonaphid transmissible due to a 

transmission-deficient coat protein was 

found to be transmitted by the aphid 

vector due to heterologous 

encapsidation when in a mixed 

infection with another potyvirus, 

papaya ringspot virus (Ref. 92). 

Heterologous encapsidation is essential 

for movement of some viruses. For 

example, umbraviruses do not encode a 

coat protein, and therefore transmission 

between plants occurs through 

encapsidation by an aphid-transmissible 

luteovirus coat protein (Ref. 93). 

Heterologous encapsidation is 

considered a possible environmental 

concern associated with PVCP-PIPs 

because of the potential that if a virus 

is heterologously encapsidated by a 

PVC-protein, the viral genome might be 

able to spread to plants the virus 

ordinarily had no means of reaching and 

thus could not have infected. 

Experimental studies have shown that 

some PVC-proteins in transgenic plants 

have the ability to encapsidate even 

unrelated infecting viruses (Refs. 94, 95, 

96, and 97). However, heterologous 

encapsidation involving a viral 

transgene can only occur if an expressed 

coat protein possesses the appropriate 

physical parameters to encapsidate the 

viral genome of infecting viruses. When 

transgenic plants containing a PVCP-PIP 

display resistance with very low or no 

levels of PVC-protein expression (e.g., 

due to PTGS), the probability of 

heterologous encapsidation would be 

very small or non-existent. (For a more 

detailed discussion of PTGS and 

suppression of gene silencing, see Unit 

II.E. above and Unit IV.F. of the 

companion document also appearing in 

today’s Federal Register.) 

Environmental concerns associated 

with heterologous encapsidation when 

PVC-protein is expressed appear to be 

largely mitigated by several factors. One, 

the heterologously encapsidated viral 

genome may not be able to replicate in 

the new host plant and could therefore 

not actually infect it. In addition, if 

replication is possible in the new plant, 

the replicating viral genome encodes for 

and thus would produce its own coat 

protein rather than that which 

heterologously encapsidated it. This 

virus would not be transmitted by the 

new vector that brought the 

heterologously encapsidated genome to 

the new host plant. The epidemiological 

consequences of such heterologous 

encapsidation would thus be limited. 

Another consideration for some viruses 

is that effective vector transmission may 

depend on more than the coat protein 

(Refs. 98 and 99), requiring regions of 

the viral genome not included in PVCPPIPs as defined for this proposal, e.g., 

coat protein read-through domains or 

helper factors. Thus, in such cases, the 

coat protein that could potentially 

heterologously encapsidate another viral 

genome would not contain all the parts 

necessary to lead to a change in vector 

specificity. In addition, in large 

monocultures of crop plants, a vector is 

most likely to move from plant to plant 

within the field and to transmit even a 

heterologously encapsidated viral 

genome to a plant that the virus is 

already able to infect (Ref. 98). Finally, 

as with recombination, as long as the 

PVC-protein expressed in the transgenic 

plant is from a virus that normally 

infects the plant in the area where it is 

planted, the outcome of any 

heterologous encapsidation that may 

occur is expected to be the same in 

transgenic plants as in natural, mixed 

infections. 

In addition to these considerations, 

EPA evaluated whether a virus that is 

heterologously encapsidated and carried 

to a new host plant might be exposed to 

a vector that feeds on the new host plant 

and perhaps other plants the virus 

ordinarily could not access. EPA 

considered whether this new vector 

might in some cases be able to transmit 

the virus even though the virus would 

now be encapsidated in its own coat 

protein, thereby expanding the virus’

vector range. A new vector could 


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possibly transfer the virus to new host 

plants, thus expanding the plant host 

range as well (Ref. 57). EPA considers 

expansion of host range through 

heterologous encapsidation to be an 

extremely unlikely outcome because 

such an outcome depends on each event 

in a series of rare events occurring. 

Should the probability of occurrence of 

any one event in this series be zero, the 

adverse event of an expanded host range 

would not occur. In addition to the 

events enumerated above, additional 

events must also occur. First, a virus 

must be heterologously encapsidated, an 

event that is possible only for some viral 

genome-coat protein combinations. 

Second, a new vector must transmit the 

encapsidated viral genome. Third, the 

transmission must be to a new host 

plant. Fourth, the heterologously 

encapsidated viral genome must be able 

to replicate in the new host plant. Fifth, 

the resulting virus, now encapsidated in 

its own coat protein, must be exposed 

to a new vector the virus never 

encountered before that is nevertheless 

able to transmit it. Finally, this vector 

must transmit the virus to a new plant 

that the virus’ prior vectors never 

visited. For such a series of events to be 

novel, the viruses, vectors, and plants 

involved must have had no previous 

opportunity to interact, and it is rare for 

such a condition to be met. For 

example, it is known that many viruses 

are transmitted by polyphagous insects, 

which would have already allowed the 

viruses to be introduced to many 

potential plant species even in the 

absence of heterologous encapsidation 

(Ref. 57). Moreover, viruses may be 

transmitted at low frequency by a range 

of species other than their primary 

vector or mechanically, e.g., through the 

practices of modern agriculture (Ref. 

98). 

Another scenario EPA considered is 

one where a high enough frequency of 

vector transmission to a new host plant 

due to heterologous encapsidation 

might mean that secondary spread 

among new plant hosts might not be 

required for the phenomenon to affect 

the population, assuming that the virus 

is able to decrease the new host plant’s 

growth and/or reproduction. Although 

this scenario may be more likely to 

occur than an expansion of host range 

given that fewer rare events would have 

to occur, any impact on the affected 

plant population would be highly 

localized being confined to plants in or 

near transgenic crop fields. Such 

negative impacts are unlikely to be 

sufficiently detrimental to require 

FIFRA regulation given their localized 

nature and the probability that common 

agricultural practices (e.g., vector 

control) could be used to manage the 

problem. Moreover, although isolated 

instances of transmission may occur, a 

significant proportion of a plant 

population is unlikely to be infected in 

such a scenario. For example, a field 

experiment (discussed in Unit 

III.D.1.iv.) showed that heterologous 

encapsidation led to infection of only 

2% of plants compared to 99% of plants 

infected under similar conditions by a 

virus that is not heterologously 

encapsidated (Ref. 100). Most 

importantly, the heterologously 

encapsidated virus will still have no 

way to spread among or beyond the 

plants of the affected population. In the 

case where a plant population contains 

relatively few individuals such that the 

impact of single plant infections would 

be magnified, plant infections are even 

less likely to occur because in addition 

to the inefficient nature of heterologous 

encapsidation, the vector would be 

more likely to feed on the more 

abundant transgenic crop plants. In 

some cases a vector may have a strong 

preference for a specific plant over even 

closely related plants (Ref. 101). 

Finally, EPA evaluated whether after 

expansion to a new host, rapid selection 

of variants best adapted to the new 

environment might lead to the evolution 

of a new virus (Ref. 57). However, in 

addition to requiring several of the rare 

events discussed above to occur, this 

phenomenon is unlikely to be entirely 

novel in any circumstance. All viruses 

that are occasionally heterologously 

encapsidated and transmitted to a new 

plant host have had the opportunity to 

adapt to new plant environments. The 

opportunities for rapid viral evolution 

presented by transgenic plants 

containing PVCP-PIPs would not be 

fundamentally different from what 

occurs in nature under reasonably likely 

circumstances. Rapid viral evolution 

after heterologous encapsidation is not 

dependent on the unique combination 

of viruses that interact but rather the 

introduction of a virus to a new plant 

host, an event that likely occurs in 

nature at some frequency for most 

viruses either through heterologous 

encapsidation or through occasional 

transmission that occurs mechanically 

or from secondary vectors (Ref. 98). 

iii. Synergy. In synergy, another type 

of viral interaction, the disease severity 

of two viruses infecting together is 

greater than expected based on the 

additive severity of each virus alone. 

For example, when a plant containing 

potato virus X (PVX) is coinfected with 

any of a number of potyviruses 

including tobacco vein mottling virus, 

tobacco etch virus, and pepper mottle 

virus, the disease symptoms are 

considerably worsened and PVX 

accumulates to a greater concentration 

(Ref. 102). A listing of reported viral 

synergisms has been compiled (Ref. 

103). 

In developing this proposal, EPA 

addressed whether synergy could occur 

between an infecting virus and a PVCPPIP, thereby increasing the severity of 

the infecting virus and whether any 

consequences for the environment could 

result from such an increase. For disease 

severity to worsen, the PVC-protein 

must be at least one of the factors 

causing synergy. However, the coat 

protein is considered much less likely to 

be responsible for synergism than other 

parts of the virus (Refs. 104 and 105), 

and a PVCP-PIP producing other viral 

proteins would not qualify for this 

proposed exemption. In addition, any 

negative effects are expected to manifest 

primarily in the transgenic crop itself. 

Furthermore, any negative effects are 

expected to be self-limiting because any 

plants containing a PVCP-PIP that is 

prone to display synergy with viruses 

common in the areas of planting would 

be quickly abandoned once such effects 

were detected, perhaps as early as the 

field-testing stage of product 

development. Synergistic interactions 

can be evaluated in transgenic plants 

before deployment by experimental 

inoculation with all of the viruses likely 

to be encountered in the field (Ref. 98). 

Developers have a strong incentive to 

undertake such efforts to ensure the 

efficacy of their product after 

deployment. 

iv. Field experiments. The 

experiments referenced in Units III.E.2.i. 

through iii. above investigated potential 

viral interactions in transgenic plants 

containing a PVCP-PIP under laboratory 

conditions. However, equally important 

is consideration of the likelihood and 

potential impact of viral interactions 

under natural field conditions (Ref. 

106). Relatively few field studies have 

been conducted to address the questions 

EPA is evaluating for this proposal, but 

the Agency has carefully considered the 

available literature in developing this 

proposed exemption. 

A 6–year experiment searched for and 

failed to find evidence of interactions 

involving viral transgenes in 25,000 

transgenic potato plants transformed 

with various PLRV coat protein 

constructs. Plants were exposed to 

infection by PLRV by direct inoculation, 

plant-to-plant spread, or natural 

exposure. In field experiments, plants 

were also naturally exposed to the 

complex of viruses that occur in the 

region. Both the greenhouse and field 

tests failed to show any change in the 


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type or severity of disease symptoms, 

and all viruses isolated were previously 

known to infect the plants and had the 

expected transmission characteristics 

(Ref. 107). These results suggest that 

viral interactions leading to evolution of 

new viruses and/or more severe viral 

disease are events too rare to be detected 

in a field trial of this size and duration. 

A 2–year experiment with transgenic 

melon and squash expressing coat 

protein genes of an aphid-transmissible 

strain of CMV failed to yield evidence 

that either recombination or 

heterologous encapsidation enabled 

spread of an aphid non-transmissible 

strain of CMV in the field (Ref. 108). A 

similar experiment used transgenic 

squash expressing coat protein genes of 

an aphid-transmissible strain of 

watermelon mosaic virus (WMV). Plants 

were mechanically inoculated with an 

aphid non-transmissible strain of 

ZYMV, and subsequent transmissions of 

the virus (assumed to be vectored by 

aphids) were assessed. Infections of 

ZYMV were not detected in 

nontransgenic fields, but the virus 

infected up to 2% of plants in 

transgenic fields. Several lines of 

evidence suggested ZYMV infection was 

mediated by the WMV PVC-protein 

heterologously encapsidating the ZYMV 

viral genome. However, the virus spread 

over short distances, and transmission 

at a low rate failed to lead to an 

epidemic of ZYMV in fields of WMVresistant transgenic squash despite the 

presence of optimal conditions for 

transmission (Ref. 100). These results 

support the contention that even if 

heterologous encapsidation involving a 

PVC-protein were to occur, the impact 

is likely to be negligible because each 

plant infection by a heterologously 

encapsidated virus requires a series of 

rare events to occur. Viral infection by 

normal routes of transmission can be at 

least an order of magnitude more 

efficient and lead to relatively greater 

impacts (Ref. 100). 

An experiment to assess the biological 

and genetic diversity of California CMV 

isolates sampled before and after 

deployment of transgenic melon 

containing the CMV coat protein gene 

documented only one CMV isolate that 

had significant sequence changes. 

However, the same change was seen 

with infection of non-transgenic plants, 

suggesting that this isolate did not result 

from recombination between the 

transgene and an infecting virus (Ref. 

109). The only field experiment to 

directly assess the effect of 

recombination in a transgenic plant 

containing a PVCP-PIP found no 

detectable grapevine fanleaf virus 

(GFLV) recombinants containing the 

inserted coat protein sequence over the 

course of a 4–year study (Ref. 110). Test 

plants consisted of nontransgenic scions 

grafted onto transgenic and 

nontransgenic rootstocks that were 

exposed over 3 years to GFLV infection 

at two locations. Analysis of challenging 

GFLV isolates revealed no difference in 

the molecular variability among isolates 

from 190 transgenic and 157 

nontransgenic plants, or from plants 

within (253 individuals) or outside (94 

individuals) of the two test sites. 

2. Proposed exemption criterion. The 

information in Units III.E.2.ii. through 

iv. suggests that heterologous 

encapsidation very rarely leads to 

changes in virus epidemiology that 

could have any large-scale impact and 

that synergy in plants containing PVCPPIPs is also unlikely to cause any 

widespread environmental harm. 

Consistent with these observations, the 

2004 SAP noted that ‘‘except perhaps 

for a very few cases, neither 

heterologous encapsidation nor synergy 

should be considered to be of serious 

concern’’ (Ref. 60). However, the 

Agency believes that in all cases, 

concerns associated with these types of 

viral interactions are likely to be limited 

in scope (for reasons discussed in Units 

III.E.2.ii. through iii.) such that the 

determination can be made that they 

pose low risk to human health and the 

environment. EPA therefore concludes 

that PVCP-PIPs present low risk with 

respect to heterologous encapsidation 

and synergy and that PVCP-PIPs could 

be exempted without further 

qualification or requirements to address 

these endpoints. 

However, EPA is not able to conclude 

at this time that all PVCP-PIPs are low 

risk with respect to recombination 

(although see Unit VII for a discussion 

of EPA’s request for information that 

might allow the Agency to reach such a 

conclusion). The Agency notes that the 

vast majority of interactions between a 

viral transgene and an infecting virus 

are expected to be no different from 

those that would occur in a natural 

mixed infection of the respective viruses 

and would not cause any adverse 

environmental effects beyond what 

could occur in the absence of the PVCPPIP. Nevertheless, the information 

discussed in Unit III.D.1.i. suggests that 

recombination among viruses may lead 

to rare instances of adverse changes in 

virus epidemiology and/or 

pathogenicity, e.g., a host range 

expansion. Based on the available 

information, EPA is not able to rule out 

that viable, recombinant viruses 

containing a portion of a PVCP-PIP 

could arise in transgenic plants and that 

in a small set of circumstances 

(discussed in Unit III.D.2.i.) such 

recombinants could be unlike those that 

could arise naturally. EPA agrees with 

the conclusions of the 2004 SAP that 

‘‘[i]n contrast to heterologous 

encapsidation and synergy, at least in 

theory, the impact of recombination 

could be much greater, since there is 

now abundant bioinformatic evidence 

that recombination has indeed, as long 

suspected, played a key role in the 

emergence of new viruses over 

evolutionary time’’ (Ref. 25). The 2005 

SAP concurred with this conclusion by 

noting that there ‘‘are a few scenarios, 

however, in which recombination may 

have an incrementally higher 

probability of creating a virus with new 

properties. In conclusion, the Panel 

recommended the need for the Agency 

to have criteria to assess the level of 

risk’’ (Ref. 11). 

The Agency notes that the 2005 SAP 

concluded that ‘‘the likelihood for 

‘novel’ interactions is very low, and the 

environmental concerns that might 

result from using PVCP-PIPs in the 

United States... is lower than that which 

occurs naturally from mixed virus 

infections’’ (Ref. 11). In addition, ‘‘it 

was repeatedly stated that the 

consequences of any recombination 

event are minimal. This conclusion was 

based on the fact that nearly every plant 

on the planet is harboring multiple virus 

infections with both closely related and 

taxonomically distinct viruses, with 

essentially no new viruses emerging 

with substantially different properties 

and causing wide pandemics or 

undesirable environmental effects’’ (Ref. 

11). In spite of such comments, EPA’s 

proposal contains § 174.27(b) because of 

the overall context of the Panel’s 

response which articulated several 

factors (discussed in Unit III.D.2.) that 

should be considered when evaluating 

recombination. EPA believes § 174.27(b) 

is consistent with these comments of the 

2005 SAP because the Agency believes 

these comments apply only when 

considering the whole set of PVCP-PIPs 

that are likely to be developed. For the 

PVCP-PIPs that would only qualify for 

an exemption without the limitations 

provided by § 174.27(b), EPA does not 

believe the Agency can conclude low 

risk with respect to recombination 

because the 2004 and 2005 SAPs have 

identified specific instances where this 

general conclusion may not hold. 

The few field evaluations conducted 

(discussed in Unit III.D.1.iv.) suggest 

that adverse environmental effects due 

to recombination in transgenic plants 

containing PVCP-PIPs are unlikely to 

occur at least on a small scale over a 

short time period. However, large 

acreages of plants containing a PVCPVerDate Aug<31>2005 17:09 Apr 17, 2007 Jkt 211001 PO 00000 Frm 00027 Fmt 4701 Sfmt 4702 E:\FR\FM\18APP2.SGM 18APP2

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PIP grown over many years may provide 

increased opportunity for rare events to 

occur that are unlikely to be detected in 

experimental studies (Ref. 104). In 

addition, none of the experimental 

systems described above would be 

predicted to involve viruses that would 

otherwise not be expected to interact in 

a mixed infection found in nature. 

Given the limited amount of field data 

available, particularly data relevant to 

the circumstances EPA has identified as 

being of highest concern (i.e., those that 

could lead to novel interactions), EPA is 

limiting the proposed exemption to 

those PVCP-PIPs for which novel viral 

interactions are unlikely to occur. When 

EPA consulted the 2004 SAP about 

situations in which novel viral 

interactions might be a concern, the 

Panel agreed ‘‘that recombination is a 

concern when the two contributing 

viruses have not previously had a 

chance to recombine’’ (Ref. 25). 

In addition to considering the 

potential for novel viral interactions to 

occur, EPA also considered whether 

transgenic plants containing PVCP-PIPs 

might have a changed frequency of viral 

interactions. The frequency could 

decrease because the cellular 

concentration of viral RNA transcripts 

expressed from transgenes may be 

orders of magnitude lower than the 

concentration of viral RNA commonly 

found in natural, mixed infections (Ref. 

111), reducing the opportunity for 

recombination. The concentration of 

infecting viral RNA from the target virus 

would also be reduced considerably if 

the PVCP-PIP is efficacious, particularly 

when the mechanism of resistance relies 

on PTGS to remove viral RNA 

transcripts with homology to the 

transgene (Ref. 112), thereby also 

reducing the opportunity for 

recombination. However, the frequency 

of interactions could also increase given 

that transgene RNA expressed from a 

constitutive promoter could be available 

for interactions with infecting viruses in 

all cells of the plant at all times - unlike 

RNA from a virus in a natural infection. 

When a virus invades a cell, it often 

replicates and then moves to other cells 

within the plant. The RNA remaining in 

the initially infected cell becomes 

encapsidated and may no longer be 

available for interactions with another 

invading virus (Ref. 113). When EPA 

presented this issue to the 2004 SAP, 

the panel responded that ‘‘no increase 

in heterologous encapsidation should be 

anticipated in PVCP-PIP plants’’ and 

‘‘the Panel believed that in general 

recombination was more likely to occur 

in transgenic plants than in nonbioengineered plants.’’ Nevertheless, the 

Panel agreed ‘‘that the important 

questions are not the relative likelihood 

for recombination to occur, but rather 

whether recombinants in transgenic 

plants are different from those in nontransgenic plants and whether they are 

viable’’ (Ref. 25). Thus, EPA’s proposal 

focuses on situations in which novel 

recombination events could occur due 

to the presence of a PVCP-PIP. 

i. Proposed categorical exemption 

criterion in § 174.27(b)(1). In developing 

the proposed categorical exemption for 

a subset of PVCP-PIPs in which a 

developer could self-determine whether 

the criteria were met, EPA sought to 

clearly identify those situations that 

pose low risk with respect to viral 

interactions. 

A PVCP-PIP would meet the viral 

interactions criterion under 

§ 174.27(b)(1) if: 

(i) The viral pathotype used to create the 

PVCP-PIP has naturally infected plants in the 

United States and naturally infects plants of 

the same species as those containing the 

PVCP-PIP, or 

(ii) The genetic material that encodes the 

pesticidal substance or leads to the 

production of the pesticidal substance is 

inserted only in an inverted repeat 

orientation or lacking an initiation codon for 

protein synthesis such that no PVC-protein is 

produced in the plant. 

Recombination between the coat 

protein gene of the PVCP-PIP and 

infecting viruses would be expected to 

be of little concern in certain instances: 

when such recombination would 

involve segments of viruses that are 

judged likely to have had the 

opportunity to recombine in a natural, 

mixed infection (and therefore any 

recombinants produced are unlikely to 

be novel), and when PTGS results in 

only small, cleaved pieces of RNA being 

available for recombination. The former 

situation would be met if the conditions 

of the criterion in proposed 

§ 174.27(b)(1)(i) are met. The latter 

situation would be met if the conditions 

of the criterion in proposed 

§ 174.27(b)(1)(ii) are met. EPA is 

proposing that no further data or 

information would be needed to 

evaluate risks associated with 

recombination when § 174.27(b)(1) is 

satisfied under either § 174.27(b)(1)(i) or 

§ 174.27(b)(1)(ii), and therefore no 

Agency review would be necessary. The 

developer may make this determination. 

If the viral pathotype used to 

construct the PVCP-PIP was isolated in 

the United States from the same plant 

species as was engineered to contain the 

PVCP-PIP, the PVCP-PIP would meet 

the proposed criterion in 

§ 174.27(b)(1)(i). It should be noted that 

this proposed criterion would be used 

in concert with the proposed protein 

production criterion in § 174.27(c) 

discussed below in Unit III.E.2., which 

ensures that any modifications from the 

natural isolate encode a protein that is 

no more than minimally modified from 

a natural virus coat protein. Thus, any 

coat protein that satisfies § 174.27(c) 

would be extremely unlikely to confer 

significantly different properties on any 

virus that could potentially acquire the 

coat protein through recombination 

with the genetic material of the PVCPPIP. 

The Agency asked the FIFRA SAP 

during the October 2004 meeting to 

what extent PVCP-PIPs in plants might 

present a potential concern should 

interactions with infecting viruses 

occur. The Panel expressed concern 

only ‘‘about certain limited situations’’

and clarified that ‘‘in most cases there 

is little a priori reason to believe that 

recombinants between viruses and 

transgenes will be more of a problem 

than recombinants between two viruses 

infecting the same plant, unless 

transgenes are derived from severe or 

exotic isolates. The general 

recommendation to use mild, endemic 

isolates as the source of the transgene 

(e.g. Hammond et al. 1999) should 

minimize any potential for creation of 

novel isolates that would not equally 

easily arise in natural mixed infections’’

(Refs. 25 and 57). The Agency’s 

proposed § 174.27(b)(1)(i) is consistent 

with this 2004 SAP recommendation 

because it excludes exotic virus isolates 

as the source of the PVCP-PIP transgene. 

Although proposed § 174.27(b)(1)(i) 

does not require that the virus isolate be 

a ‘‘mild’’ form of the virus, it does 

ensure that when virus isolates capable 

of causing severe cases of viral disease 

are used, the PVCP-PIP may only meet 

§ 174.27(b)(1)(i) if the viral pathotype 

was present in the natural system and 

therefore should pose no risk of novel 

interactions. 

The 2005 SAP offered a decision 

flowchart indicating a point at which 

the Agency should identify the few 

scenarios where recombination may be 

of concern: ‘‘the question arises as to 

whether recombination of the sequence 

could lead to a significant change in the 

properties of the recombinant over the 

original properties of the superinfecting 

virus. Significant changes include 

increase in pathogenicity, increase of 

host range or change of vector’’ (Ref. 11). 

EPA believes that consideration of 

whether the conditions of proposed 

§ 174.27(b)(1)(i) are met addresses 

whether the potential exists for 

significant changes in the properties of 

a recombinant virus compared to what 


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might occur in a natural, mixed 

infection. 

In addition to excluding exotic virus 

isolates, proposed § 174.27(b)(1)(i) also 

excludes PVCP-PIPs that are inserted 

into a plant species that is not naturally 

infected by the virus used to create the 

PVCP-PIP. Most PVCP-PIPs are created 

from viruses that do naturally infect the 

plant species into which they are 

inserted because greater efficacy is 

achieved when a virus most similar to 

the target virus is used as the source of 

the sequence used in the PVCP-PIP. 

However, virus-resistant transgenic 

plants have been created where this is 

not the case (Ref. 114). In these 

situations, a virus is introduced into a 

system where it does not naturally 

occur, and viruses with which it does 

not otherwise interact may be present in 

that system. The Agency cannot a priori 

determine that such interactions are safe 

because there is no experience upon 

which to base such a finding. 

Proposed § 174.27(b)(1)(i) is also 

consistent with the 2005 SAP’s 

recommendation to consider ‘‘whether 

recombination of the sequence could 

lead to a significant change in the 

properties of the recombinant over the 

original properties of the superinfecting 

virus’’ (Ref. 11). When the viral 

pathotype used to create the PVCP-PIP 

has naturally infected plants in the 

United States and naturally infects 

plants of the same species as those 

containing the PVCP-PIP, the sequences 

that could interact would be expected to 

already have opportunities to interact in 

nature and thus no novel recombinants 

should be produced. 

The Agency’s proposed 

§ 174.27(b)(1)(ii) is consistent with the 

2005 SAP’s recommendation to consider 

whether the PVCP-PIP expresses PVCprotein when evaluating the potential 

consequences of recombination (Ref. 

11). When a PVCP-PIP expresses no 

PVC-protein because it is designed to 

mediate resistance through PTGS, 

recombination would be of little 

concern because ‘‘recombination 

between a full-length viral RNA and a 

cleaved small RNA resulting from PTGS 

would yield a truncated non-functional 

RNA. Therefore, a PTGS transgene poses 

negligible potential to yield novel 

recombinant viruses’’ (Ref. 11). EPA 

therefore makes part of its proposal two 

circumstances when, according to the 

2005 SAP, the PVCP-PIP can only 

mediate resistance through PTGS 

because it would produce no PVCprotein: when the genetic material that 

encodes the pesticidal substance or 

leads to the production of the pesticidal 

substance is inserted only in an inverted 

repeat orientation or lacking an 

initiation codon for protein synthesis 

such that no PVC-protein is produced in 

the plant (Ref. 11). See Unit III.D.2.ii. 

below for a discussion of how other 

constructs mediating resistance through 

PTGS could meet § 174.27(b). 

One Panel member noted, ‘‘PTGS 

results in small RNA from the PIP and 

the infecting virus that could, in certain 

circumstances, be recombinatorial.’’

However, the Panel concluded ‘‘this 

minimal RNA would not confer a 

phenotype to the recombinant, would 

result in just a few nucleotide changes 

in a potential recombinant, and thus 

would be irrelevant’’ (Ref. 11). 

EPA proposes to define the term 

‘‘naturally infect’’ to mean ‘‘to infect by 

transmission to a plant through direct 

plant-to-plant contact (e.g., pollen or 

seed), an inanimate object (e.g., farm 

machinery), or vector (e.g., arthropod, 

nematode, or fungus). It does not 

include infection by transmission that 

occurs only through intentional human 

intervention, e.g., manual infection in a 

laboratory or greenhouse setting.’’ The 

Agency is proposing this definition 

specifically to exclude transmission that 

occurs only through intentional human 

intervention because such transmission 

would have little relevance to normal 

virus infection. EPA recognizes that 

humans may play an inadvertent role in 

infection (e.g., by transmitting the virus 

on farm machinery). Such unintentional 

(and often unavoidable) transmission 

can be an important means of virus 

transmission, leading to the natural 

presence of viruses in plants. EPA 

therefore proposes to include this mode 

of incidental transmission in the 

definition of naturally infect. 

EPA uses the term ‘‘viral pathotype’’

rather than the more generic term 

‘‘virus’’ in response to the October 2004 

FIFRA SAP comment that ‘‘[n]ot all 

isolates of a virus infect and cause 

disease in all plant genotypes and, as a 

consequence, the unqualified use of the 

term ‘virus’ when setting a condition for 

applicants to the Agency [is] not 

adequate in this context. It is therefore 

appropriate in the context of biosafety 

as well as virus epidemiology to 

recognize the value of defining specific 

viral pathotypes or host range variants.’’

The 2005 SAP was asked to comment on 

the use of this term and responded, 

‘‘there was not much discussion of this 

term. The Panel suggested that logic 

says that local or indigenous virus 

isolates, or those with significant 

sequence similarity, will be used to 

generate PVCP-PIPs. From what we 

know now, only those viruses with high 

sequence identity will be useful as 

sources of the PVCP-PIP transgene.’’

EPA agrees that generally viral 

pathotypes that meet § 174.27(b)(1) will 

be those most effective for creating 

PVCP-PIPs and will therefore be the 

most commonly used. However, EPA 

considers the limitations imposed by 

this term to be necessary because the 

Agency cannot conclude that viruses 

not meeting this criterion would be low 

risk with respect to recombination. 

In this proposed criterion and in 

§ 174.27(c) discussed below, EPA uses 

the phrase ‘‘genetic material that 

encodes the pesticidal substance or 

leads to the production of the pesticidal 

substance,’’ rather than the phrase 

‘‘genetic material necessary for the 

production,’’ to indicate that regulatory 

regions, such as promoters, enhancers, 

or terminators, need not be considered 

in evaluating whether a PVCP-PIP 

satisfies these criteria. EPA is not 

proposing to amend the definitions for 

‘‘genetic material necessary for the 

production’’ or ‘‘regulatory region,’’

both found at 40 CFR 174.3, and is not 

seeking any comment on these 

definitions. 

ii. Proposed exemption criterion 

conditional on Agency determination in 

§ 174.27(b)(2). The Agency recognizes 

that many PVCP-PIPs may pose low risk 

with respect to recombination even 

though they fail to satisfy § 174.27(b)(1). 

Therefore, EPA is proposing an 

approach under which PVCP-PIPs that 

fail to meet § 174.27(b)(1) could still 

meet § 174.27(b), subject to an Agency 

review to determine whether they meet 

a different set of conditions related to 

this issue. Under this proposed 

approach, a PVCP-PIP would meet 

§ 174.27(b) under § 174.27(b)(2) if the 

Agency determines that viruses that 

naturally infect the plant containing the 

PVCP-PIP are unlikely to acquire the 

coat protein sequence through 

recombination and produce a viable 

virus with significantly different 

properties than either parent virus. 

The conditions in proposed 

§ 174.27(b)(1) address the potential for 

recombinants to arise unlike those 

expected in natural mixed infections 

primarily by ensuring that no novel 

viral interactions occur. Under proposed 

§ 174.27(b)(2), a PVCP-PIP could qualify 

for exemption even when novel viral 

interactions could occur providing steps 

were taken to ensure that an infecting 

virus would not acquire a portion of the 

PVCP-PIP coat protein sequence through 

recombination and produce a viable 

virus with significantly different 

properties than either parent virus. 

Experimental evidence has suggested 

a number of ways coat protein genes of 

certain viruses may be modified in 

constructing a PVCP-PIP to reduce the 

possibility they would participate in a 


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recombination event with an infecting 

virus. For example, removing the 3′ 

untranslated region (UTR) in the coat 

protein mRNA transcript may be 

effective at reducing recombination for 

viruses that carry the initiation 

promoters of RNA replication in this 

region (Ref. 115). Evidence suggests that 

recombination among RNA viruses 

occurs via template switching by the 

viral replicase during replication such 

that a hybrid molecule is formed (Ref. 

116). Inclusion of the 3′ UTR may 

enable replication to begin on the 

mRNA transcript and then switch to the 

RNA of the invading virus. Removal of 

this region would necessitate two 

separate template-switching events to 

form a successful recombinant and thus 

reduce its likelihood of occurrence (Ref. 

80). Experiments with CCMV 

demonstrated that deletions in the 3′ 

UTR did indeed reduce the recovery of 

recombinant viruses (Ref. 117). Since 

functional resistance is still conferred 

by constructs containing a CP lacking 

the 3′ UTR, this region may not be 

necessary. Other techniques that have 

been suggested include: 

• Reducing the extent of shared 

sequence similarity between the 

infecting virus and the transgene to 

reduce the opportunities for 

homologous recombination (Ref. 118). 

• Excluding any sequences 

containing replicase recognition sites 

that are potential sites of recombination 

and any sequences known or thought to 

be recombination hotspots, e.g., 

promoters for genomic and subgenomic 

RNA synthesis (Ref. 119). 

• Avoiding potential hairpin 

structures in the transgene that might 

function as acceptor structures for the 

replicase complex (Ref. 120). 

It is important to note that any PVCprotein produced must be evaluated 

under § 174.27(c) in order for the PVCPPIP to qualify for exemption. Some 

techniques that may enable a PVCP-PIP 

to meet § 174.27(b)(2) would preclude 

the PVCP-PIP from meeting 

§ 174.27(c)(1) and necessitate a review 

under § 174.27(c)(2). For example, a 

construct could meet proposed 

§ 174.27(b)(2) if it contained portions of 

several different coat protein genes in 

tandem, linked together in such a way 

that if the sequence were translated it 

would yield a non-functional coat 

protein of no use to a virus. A virus that 

acquired this entire sequence through 

recombination in exchange for portions 

of its own genome would likely be 

nonviable. As another example, a 

construct might meet proposed 

§ 174.27(b)(2) if it contained a very 

small portion of a coat protein gene. In 

such cases, a virus would be unlikely to 

acquire this sequence through 

recombination without picking up 

additional pieces of genetic material 

from the construct or the plant genome 

that would likely render the virus 

nonviable. Or, if a virus did acquire a 

piece of just the small part of the coat 

protein sequence contained in the 

transgenic plant, it would likely not be 

large enough to significantly change the 

properties of the parent virus. Any PVCprotein produced from either such 

construct would fail to meet 

§ 174.27(c)(1) but could be evaluated 

under and may nevertheless meet 

§ 174.27(c)(2) (see Unit III.E.2. below). 

EPA recognizes the comments of the 

2004 SAP that ‘‘methods for minimizing 

recombination are only partially 

effective. For this reason, the question 

remains whether novel recombinants 

would be created in transgenic plants, 

and simply reducing the frequency of 

these events is not an answer to the 

question’’ (Ref. 60). However, EPA 

believes that a combination of two or 

more methods, or even perhaps a single 

method in some cases, could be 

employed to reduce the expected 

frequency of recombination such that 

the Agency would be able to make a 

determination that a PVCP-PIP would 

pose low risk with respect to viral 

interactions. EPA asked the 2004 SAP 

‘‘which methods are sufficiently 

effective such that requiring 

measurement of recombination rates 

would be unnecessary. The Panel 

doubted if the... methods [discussed] are 

sufficiently effective to warrant the 

reduction of recombination rates below 

the level that the actual measurement 

will be unnecessary’’ (Ref. 25). 

However, the Agency would have the 

opportunity during the case-by-case 

Agency review under § 174.27(b)(2) to 

consider the particular viral system and 

whether literature supports the 

contention that the recombination 

reduction techniques are likely to be 

sufficiently effective in the system in 

which they are employed. EPA 

anticipates that the Agency could base 

this determination on the expected 

reduction in frequency of recombination 

as determined from the literature and 

that actual measurement of 

recombination rates may be 

unnecessary. Given that there is no 

universally applicable method for 

reducing recombination frequency and 

this type of case-by-case consideration 

of the particular virus system in 

question must be conducted, EPA 

believes an Agency review is needed to 

make this determination. With an 

Agency determination under 

§ 174.27(b)(2), EPA would create a 

criterion that would encompass a larger 

set of those PVCP-PIPs that pose low 

risk with respect to viral interactions 

than are covered under § 174.27(b)(1). 

Section 174.27(b)(2) is consistent with 

the advice of the 2005 SAP in that it 

incorporates the portions of the 

proposed decision tree that allow 

consideration of whether there are 

‘‘features controlling recombination,’’

whether ‘‘the protein [is] complete,’’

and whether the plant host contains 

‘‘genes that reduce recombination’’ (Ref. 

11). Likewise, the review procedures for 

determining whether a PVCP-PIP met 

the conditions of § 174.27(b)(2) would 

also be able to consider ‘‘the type of 

RNA-dependent RNA polymerase 

(RdRps) encoded by the superinfecting 

virus and the compartmentalization of 

its site of replication’’ as suggested by 

the 2005 SAP (Ref. 11). Although EPA 

notes that there was some disagreement 

among the Panel members about the 

appropriateness of including such 

information as part of the flow chart, the 

Agency believes that this information 

could be reasonably considered when 

available and when sufficient 

knowledge about the plant/virus system 

exists such that it would offer useful 

information for evaluating this criterion. 

Overall, § 174.27(b) thus enables the 

Agency to consider either under 

§ 174.27(b)(1) or § 174.27(b)(2) all of the 

factors mentioned in the flowchart by 

the 2005 SAP. 

3. Historical approaches still under 

consideration. EPA’s proposed 

exemption in 1994 did not contain any 

criteria related to viral interactions. 

However, since that time, many 

additional scientific papers and reviews 

have been published on this topic. Most 

affirm the general safety of PVCP-PIPs 

with respect to viral interactions, but 

some call into question assumptions of 

how generically this conclusion holds 

across all PVCP-PIPs. For example, 

although the 2000 NRC report stated 

that ‘‘[m]ost virus-derived resistance 

genes are unlikely to present unusual or 

unmanageable problems that differ from 

those associated with traditional 

breeding for virus resistance,’’ the NRC’s 

report also suggested that their 

conclusions were based on the 

assumption that certain risk 

management strategies should or would 

be implemented, e.g., elimination of 

specific sequences to limit the potential 

for recombination (Ref. 10). EPA 

believes the Agency’s 1994 conclusion 

of low probability of risk still holds for 

most PVCP-PIPs. However, in order to 

grant an exemption under FIFRA, EPA 

must be able to make such a finding for 

all PVCP-PIPs covered by the exemption 

and must make its safety determination 


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in the absence of any regulatory 

oversight under FIFRA that could 

ensure mitigation measures, such as 

those discussed in the NRC report, were 

employed. Therefore, it appears prudent 

at this time to limit this proposed 

exemption with a criterion that restricts 

the potential for novel recombination 

events, as these have been identified as 

the rare situation in which viral 

interactions in plants containing a 

PVCP-PIP may lead to adverse 

environmental effects. 

EPA presented a set of conditions to 

the 2004 SAP and asked whether they 

would significantly reduce either the 

novelty or frequency of viral 

interactions in plants containing PVCPPIPs such that the Agency would not 

need to regulate the PVCP-PIP (Ref. 25). 

The first proposed condition was that 

‘‘the genetic material of the PVCP-PIP is 

translated and/or transcribed in the 

same cells, tissues, and developmental 

stages naturally infected by every virus 

from which any segment of a coat 

protein gene used in the PVCP-PIP was 

derived.’’ EPA considered such a 

condition because with a PVCP-PIP, 

plants may express viral genes in cells 

and/or tissues that the virus does not 

normally infect. Genetic promoters 

currently used in most transgenic plants 

cause constitutive expression of 

transgenes at developmental stages that 

might otherwise be unaffected by viral 

infection and often in tissues that the 

virus does not normally infect (Ref. 

113). For example, luteoviruses are 

normally expressed only in phloem 

tissue, but the cauliflower mosaic virus 

(CaMV) promoter, commonly found in 

existing PIP constructs, would drive 

expression of luteoviral coat protein in 

all plant cells. Some evidence suggests 

that in natural infections different 

viruses have different temporal or 

spatial expression patterns that would 

limit their interactions (Refs. 63, 121, 

and 122). However, the 2004 SAP 

concluded that such a condition would 

be of limited utility because ‘‘[m]ost 

plant viruses are present in a wide range 

of cell and tissue types’’ (Ref. 25). 

The second condition proposed to the 

2004 SAP was that ‘‘the genetic material 

of the PVCP-PIP contains coat protein 

genes or segments of coat protein genes 

from viruses established throughout the 

regions where the crop is planted in the 

United States and that naturally infect 

the crop into which the genes have been 

inserted.’’ EPA considered the first part 

of this criterion because plants may be 

engineered with coat protein genes from 

an exotic strain of a virus that may be 

more virulent or have other properties 

different from endemic isolates. 

Interactions between a PVCP-PIP based 

on such virus sequences and infecting 

viruses could potentially change the 

epidemiology or pathogenicity of the 

infecting viruses. The 2004 SAP 

concurred that ‘‘using such an exotic 

coat protein gene would open 

possibilities for novel interactions.’’

EPA’s current proposed § 174.27(b) thus 

excludes from exemption PVCP-PIPs 

based on coat protein genes from exotic 

viruses unless steps have been taken to 

reduce the frequency of recombination. 

EPA considered the second part of 

this 2004 criterion (i.e., the genetic 

material of the PVCP-PIP contains coat 

protein genes or segments of coat 

protein genes from viruses... that 

naturally infect the crop into which the 

genes have been inserted) because in 

heterologous resistance a plant may be 

resistant to infection by a particular 

virus in spite of having the coat protein 

gene of another virus incorporated into 

its genome. For example, coat protein 

genes from LMV were used to provide 

resistance to PVY in tobacco which is 

not infected by LMV (Ref. 114). In such 

plants, LMV sequences might have a 

new opportunity to interact with viruses 

that infect tobacco. The 2004 Panel 

concluded that ‘‘[w]hat is described 

here is most often implemented: in 

designing a PVCP transgene, better 

efficacy is often observed if it is as 

similar as possible to the target virus.’’

Nevertheless, EPA believes that EPA’s 

current proposed criterion (b) is 

appropriate given that PVCP-PIPs may 

be developed using heterologous 

resistance. This criterion excludes from 

exemption PVCP-PIPs used in plants 

that the virus used to create the PVCPPIP does not naturally infect unless 

steps have been taken to reduce the 

frequency of recombination. 

The third condition proposed to the 

2004 SAP was that ‘‘the PVCP-PIP has 

been modified by a method 

scientifically documented to minimize 

recombination (e.g., deletion of the 3′ 

untranslated region of the coat protein 

gene). As discussed above, the 2004 

SAP expressed reservation about such a 

criterion, and EPA recognizes that any 

single method for minimizing 

recombination may be only partially 

effective (Ref. 60). However, EPA 

believes that a combination of two or 

more methods, or even perhaps a single 

method in some cases, could be 

employed such that the expected 

frequency of recombination would be 

reduced to a level that would support 

determination that a PVCP-PIP would 

pose low risk with respect to viral 

interactions, but that such a 

determination could only be made on a 

case-by-case basis. EPA thus intends 

that the proposed criterion in 

§ 174.27(b)(2)(ii) would allow the 

Agency to make this determination after 

review. 

The fourth condition proposed to the 

2004 SAP was that ‘‘the PVCP-PIP has 

been modified by a method 

scientifically documented to minimize 

heterologous encapsidation or vector 

transmission, or there is minimal 

potential for heterologous encapsidation 

because no protein from the introduced 

PVCP-PIP is produced in the transgenic 

plant or the virus does not participate in 

heterologous encapsidation in nature.’’

The 2004 SAP concluded that ‘‘[t]his 

method can... be considered seriously if 

deemed necessary’’ (Ref. 25). However, 

the Agency concluded (as discussed 

above in Unit III.D.1.ii.) that such 

methods are not necessary because 

heterologous encapsidation is so rarely 

likely to be of any significant ecological 

concern. 

Based on these considerations, EPA 

presented a set of modified conditions 

to the 2005 SAP that reflected the 

advice of the 2004 SAP. Those 

conditions were the same as those that 

EPA is proposing today in § 174.27(b) 

except that § 174.27(b)(2) as submitted 

to the 2005 SAP included an additional 

provision: this criterion could be met by 

meeting the current conditions or by 

meeting the condition that ‘‘the 

properties of the viral pathotype that are 

determined by the coat protein gene 

used to create the PVCP-PIP are 

substantially similar to the properties of 

a viral pathotype that naturally infects 

plants in the United States, and the viral 

pathotype used to create the PVCP-PIP 

naturally infects plants of the same 

species as that containing the PVCPPIP.’’ EPA is no longer proposing this 

condition as a means of meeting 

§ 174.27(b) because the 2005 SAP 

concluded that it was ‘‘unusable and 

cannot be re-written into a satisfactory 

form’’ because of the difficulty of 

defining ‘‘properties’’ and ‘‘substantially 

similar’’ in this context (Ref. 11). 

E. Production of Proteins 

1. Scientific issues. In addition to 

weediness and viral interactions, a third 

concern associated with PVCP-PIPs 

relates to the potential production of 

proteins (called PVC-proteins) from the 

plant virus coat protein sequences of the 

PVCP-PIP, i.e., the potential for human 

or nontarget organism exposure to 

proteins that have not previously 

existed in nature and thus should be 

examined to determine whether they 

have potentially toxic or allergenic 

properties. EPA must consider the safety 

of any potentially expressed proteins 

that are part of the PIP when proposing 


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19620 Federal Register / Vol. 72, No. 74 / Wednesday, April 18, 2007 / Proposed Rules 

criteria to evaluate PVCP-PIPs for 

possible exemption. 

EPA considered human dietary, 

human occupational, and nontarget 

exposure risks in evaluating the safety 

of PVC-proteins for purposes of this 

proposal as the Agency must do when 

evaluating whether a pesticide can be 

exempt from the requirements of FIFRA. 

See EPA’s assessment of human dietary 

exposure risks and other nonoccupational exposure risks published 

in the companion document in today’s 

Federal Register that proposes to 

establish a tolerance exemption under 

FFDCA section 408 for residues of the 

PVC-protein portion of a PVCP-PIP. 

Many, if not all, of the considerations 

used to evaluate the potential for novel 

occupational or nontarget exposures can 

be directly extrapolated from the 

discussion in this companion document 

describing EPA’s base of experience 

with viruses infecting food plants. That 

analysis led the Agency to draw three 

conclusions on which it is relying to 

support the proposed tolerance 

exemption for residues of PVC-proteins 

in food and which can also be used to 

support this proposed criterion for 

exemption from FIFRA requirements. 

First, virus-infected plants have always 

been a part of the human and domestic 

animal food supply. Most crops are 

frequently infected with plant viruses, 

and food from these crops has been and 

is being consumed without adverse 

human or animal health effects. Second, 

plant viruses are not infectious to 

humans, including children and infants, 

or to other mammals. Third, plant virus 

coat proteins, while widespread in food, 

have not been associated with toxic or 

allergenic effects to animals or humans. 

EPA derived these conclusions from a 

sufficient experience and information 

base to support the proposed tolerance 

exemption and this proposed criterion 

for exemption from FIFRA 

requirements. 

EPA consulted the 2004 SAP about 

possible nontarget effects of PVCproteins and the validity of the Agency’s 

risk assessment being based on the 

known history of safe exposure to coat 

proteins of naturally occurring plant 

viruses. Virus infected plants have 

always been a part of the natural 

environment, and organisms that 

interact with plants have likely been 

exposed to plant virus coat proteins 

over long periods of time. The panel 

confirmed that PVC-proteins within the 

range of natural variation of the virus 

would not be anticipated to present 

risks to nontarget organisms, concluding 

that, ‘‘[l]ethal effects in animal life after 

feeding on PVCP-PIP plants are highly 

unlikely because plant viruses are not 

known to have deleterious effects on 

animal life. Additionally, animals 

routinely feed on non-engineered virusinfected plants and do not die.... 

[S]ublethal effects are not expected to be 

manifested in animal life, again because 

wildlife and insects regularly feed on 

non-engineered virus-infected plants 

with no apparent sublethal damage’’

(Ref. 60). 

The 2005 SAP echoed these general 

conclusions by pointing out that virus 

coat proteins ‘‘are naturally present in 

the environment and no adverse effects 

to humans or non-targets have been 

reported’’ (Ref. 11). However, the 2005 

SAP also suggested that additional 

concerns might warrant evaluation, 

including ‘‘indirect ecological effects 

(such as altered food sources, vegetative 

cover, or microbial communities)’’ (Ref. 

11). The particular concerns associated 

with such effects were not articulated. 

PVC-proteins that meet the conditions 

of this exemption are not expected to 

alter nontarget food sources because 

they would be so similar to plant virus 

coat proteins that occur naturally. 

Indirect effects such as changes in 

vegetative cover might occur if crop 

plants containing a PVCP-PIP are larger 

and/or more productive in the absence 

of virus infection relative to plants that 

are infected. However, the overall effect 

on nontarget organisms is still likely to 

be minor given that crops are often 

grown in the absence of viral disease 

even without the use of a PVCP-PIP, and 

PVCP-PIPs exempted by this proposal 

would have very limited ability to 

spread from crop plants to wild or 

weedy relatives. PVCP-PIPs are not 

expected to impact microbial 

communities because natural plant 

virus coat proteins are not known to 

have any toxic mode of action. 

Moreover, plant virus coat proteins 

already occur naturally in the 

environment so microbial communities 

are already exposed to such proteins. 

Some Panel members also ‘‘expressed 

concern over potential effects on 

pollinators,’’ but EPA is unaware of any 

scientific evidence supporting this 

concern. EPA concurs with other Panel 

members who believed that ‘‘a history of 

exposure by pollinators to naturally 

infected plants can be taken as 

indicating that there are no novel risks’’

(Ref. 11). 

Other concerns raised by the 2005 

SAP regarding nontarget and human 

non-dietary exposure are addressed in 

the companion document published in 

today’s Federal Register, where they are 

discussed in the context of 

consideration of the human dietary risks 

associated with PVC-proteins. The 

companion document describes in Unit 

IV.C., for example, the basis for EPA’s 

conclusion that the hazard associated 

with PVC-proteins that meet § 174.27(c) 

of this proposed exemption is 

sufficiently low that they do not rise to 

the level warranting regulation. These 

same arguments can be applied to PVCproteins that meet § 174.27(c) in this 

proposal, even in the rare cases when 

nontarget exposure to a PVC-protein 

might be greater than the exposure to 

the corresponding natural plant virus 

coat protein. The companion document 

also describes in Unit IV.C. rationales 

that can be used to support EPA’s 

conclusion that nontarget exposure to 

PVC-proteins in plant tissues that do not 

normally contain the corresponding 

plant virus coat protein is unlikely to 

contribute significantly to risk. 

Nontarget organisms would be exposed 

to natural plant virus coat proteins 

through a variety of routes and there is 

no evidence that they would be toxic to 

any nontarget organisms regardless of 

the route of exposure. 

2. Proposed exemption criterion. As 

with the other proposed criteria 

discussed in this document, EPA is 

proposing that § 174.27(c) would have 

two parts: Section 174.27(c)(1) under 

which a developer may self-determine if 

a PVCP-PIP meets the conditions, and 

§ 174.27(c)(2) under which the Agency 

must make the determination. 

i. Proposed categorical exemption 

criterion in § 174.27(c)(1). In developing 

the proposed categorical exemption for 

a subset of PVCP-PIPs in which a 

developer could self-determine whether 

the criteria were met, EPA sought to 

identify clearly those situations that 

pose low risk with respect to protein 

production because any PVC-proteins 

produced would be within the range of 

natural variation. EPA wants to ensure 

that a long history of safe human and 

nontarget exposure has occurred for any 

PVC-protein produced from a PVCP-PIP 

that could qualify for this exemption. A 

PVCP-PIP would meet § 174.27(c)(1) if a 

product developer self-determines that: 

The genetic material that encodes the 

pesticidal substance or leads to the 

production of the pesticidal substance: 

(i) Is inserted only in an inverted repeat 

orientation or lacking an initiation codon for 

protein synthesis such that no PVC-protein is 

produced in the plant, or 

(ii) Encodes only a single virtually 

unmodified viral coat protein. Multiple PVCproteins could each separately meet this 

criterion. Chimeric PVC-proteins do not 

qualify. 

EPA intends with the phrase ‘‘is 

inserted only in an inverted repeat 

orientation or lacking an initiation 

codon for protein synthesis such that no 

PVC-protein is produced in the plant’’


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2The concern relating to the need for an 

allergenicity assessment is relevant to the Agency’s 

determinations concerning occupational exposures. 

to include only those PVCP-PIPs with 

the specified types of constructs that the 

2005 SAP indicated provide a high 

degree of certainty that no PVC-protein 

would be produced. Although other 

types of constructs may also usually not 

produce any PVC-protein, EPA believes 

it is necessary to incorporate into its 

proposal a provision for an Agency 

review of such constructs. In such a 

review, EPA could evaluate the level of 

protein production, if any, that could 

occur under a variety of circumstances 

and environmental conditions 

representative of those that the plant 

may experience (see Unit III.E.2.ii.). 

EPA includes the word ‘‘only’’ and the 

phrase ‘‘such that no PVC-protein is 

produced in the plant’’ in 

§ 174.27(c)(1)(i) to ensure that the 

proposed exemption encompasses only 

those PVCP-PIPs that the 2005 SAP 

indicated ‘‘could be safely determined 

to have no [PVC-protein] expression 

regardless of plant tissue, 

developmental stage, environmental 

conditions, or exposure to virallyencoded suppressors of PTGS’’ (Ref. 11). 

The proposed exemption criterion in 

§ 174.27(c)(1)(i) would not be met by a 

PVCP-PIP when there are multiple-copy 

insertions in the plant if any of the 

copies is not in an inverted repeat 

orientation or lacking an initiation 

codon for protein synthesis. 

The Agency proposes to define the 

term ‘‘unmodified’’ to mean, ‘‘having or 

coding for an amino acid sequence that 

is identical to an entire coat protein of 

a naturally occurring plant virus. The 

Agency proposes to define the term 

‘‘virtually unmodified’’ to mean, 

‘‘having or coding for an amino acid 

sequence that is identical to an entire 

coat protein of a naturally occurring 

plant virus, except for the addition of 

one or two amino acids at the N- and/ 

or C-terminus other than cysteine, 

asparagine, serine, and threonine and/or 

the deletion of one or two amino acids 

at the N- and/or C-terminus.’’ EPA’s 

rationale for these proposed definitions 

and alternative proposals for defining 

‘‘virtually unmodified’’ are found in the 

companion document published in 

today’s Federal Register. The alternative 

proposals for virtually unmodified will 

also be considered as alternatives under 

this FIFRA proposal. 

EPA is proposing to exclude more 

significantly modified PVC-proteins 

from the proposed categorical 

exemption by requiring that the genetic 

material encode ‘‘only a single virtually 

unmodified viral coat protein.’’ For 

example, PVC-proteins containing 

internal insertions, deletions, or amino 

acid substitutions would be excluded, 

as would be chimeric proteins that are 

encoded by a sequence constructed from 

portions of two or more different plant 

virus coat protein genes. EPA is 

proposing to exclude such PVC-proteins 

from the self-determining part of the 

exemption in response to the advice of 

the FIFRA SAP in October 2004 that, 

‘‘[t]here was general agreement that an 

allergenicity assessment2 would be 

appropriate for insertions or deletions, 

except perhaps for terminal deletions 

that do not affect overall protein 

structure.’’ Insufficient information 

exists at this time to allow EPA to 

describe a priori a criterion that would 

ensure all PVC-proteins with 

modifications other than those 

encompassed by the definition of 

‘‘virtually unmodified’’ fall within the 

base of experience supporting the 

proposed exemption. At this time, it is 

not possible to make a categorical risk 

assessment finding that other types of 

changes are unlikely to change the 

characteristics of any protein produced. 

Thus, EPA proposes no other 

modifications be allowed in PVCproteins that would meet § 174.27(c)(1). 

EPA intends that multiple PVCproteins expressed in the same plant 

could each separately meet the criterion 

in § 174.27(c)(1)(ii) but that chimeric 

PVC-proteins could not meet this 

criterion. Chimeric proteins would 

include PVC-proteins composed of the 

fusion of two (or more) whole or partial 

capsid proteins, as well as chimeric 

proteins that contain a PVC-protein 

fused with another, unrelated protein. 

The 2005 SAP concluded that such 

chimeric proteins could possibly have 

‘‘completely different antigenic and 

possibly allergenic properties compared 

to the properties of the individual 

capsid proteins’’ (Ref. 11). EPA is 

therefore unable to conclude that such 

proteins would be low risk without a 

case-by-case review of the protein. EPA 

intends that multiple, distinct PVCproteins produced, for example, from a 

single transgene insertion event or from 

multiple insertion events in the same 

plant, could qualify for this exemption 

because the Agency believes that the 

properties of each individual protein 

would be the relevant factors to 

consider. Some members of the 2005 

SAP believed that ‘‘EPA evaluations 

should consider effects of multiple 

constructs of PVCP-PIPs introduced in 

transgenic plants’’ (Ref. 11). The 

rationale for this concern appears based 

in part on the potential for a synergistic 

effect from multiple toxins. However, 

PVC-proteins produced from a PVCPPIP that could qualify for this 

exemption would not be expected to 

have any toxic mode of action that 

could cause such a phenomenon. The 

rationale for this concern appears to be 

also based in part on the potential for 

multiple PVC-proteins to ‘‘alter ‘natural’

protein production in plants’’ (Ref. 11). 

However, EPA concurs with other 2005 

SAP members who ‘‘believed that this 

situation was no different than is likely 

to occur in nature, where a plant might 

be infected by multiple unrelated 

viruses’’ (Ref. 11). (See also Unit IV.E.1. 

in the companion document published 

in today’s Federal Register for the basis 

for EPA’s conclusion that exposure to 

plants with different levels of proteins 

elicited by pathogen attack, wounding, 

or stress, i.e., ‘‘pathogenesis-related 

proteins,’’ likely occurs normally.) 

EPA believes the phrase ‘‘an entire 

coat protein’’ in the definition of 

‘‘virtually unmodified’’ conveys that 

segments of PVC-proteins do not meet 

the criterion in § 174.27(c)(1)(ii). This 

limitation is based on the advice of the 

2005 SAP that ‘‘[d]etermining whether 

PVC-proteins containing terminal 

deletions, or any other modifications, 

are within the range of natural variation 

would require the development of a 

database of the natural variation and 

truncated forms of PVC-proteins that 

occur naturally.’’ As such, EPA could 

more appropriately take this 

consideration into account under the 

criterion in § 174.27(c)(2)(i) which 

contains provisions for an Agency 

review (discussed below in Unit 

III.E.2.ii.). However, EPA is considering 

several alternative definitions for 

‘‘virtually unmodified,’’ some of which 

may allow truncated PVC-proteins to 

meet the proposed criterion in 

§ 174.27(c)(1)(ii). These alternatives are 

presented and discussed in Unit IV.E.1. 

of the companion document published 

elsewhere in today’s Federal Register. 

If the genetic material that encodes 

the pesticidal substance or leads to the 

production of the pesticidal substance 

encodes only a single virtually 

unmodified viral coat protein, no novel 

exposures to humans or nontarget 

organisms are likely to occur because 

these PVC-proteins are essentially 

identical to plant viral coat proteins that 

are widespread in the plant kingdom, as 

most plants are susceptible to infection 

by one or more viruses. EPA is relying 

on this history of safe exposure to 

support this proposal. The Agency 

believes that when such a PVCP-PIP is 

used, the PVCP-PIP would pose low 

probability of risk with respect to 

protein production. EPA is proposing 

that no further data or information 

would be needed to evaluate this issue 


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when § 174.27(c)(1) is satisfied, and 

therefore no Agency review would be 

necessary. 

ii. Proposed exemption criterion 

conditional on Agency determination in 

§ 174.27(c)(2). The Agency 

acknowledges that many PVCP-PIPs 

may pose low risk with respect to 

concerns associated with protein 

production even though they fail to 

satisfy § 174.27(c)(1). EPA is proposing 

to review such PVCP-PIPs under slightly 

different factors that the Agency 

believes also ensure that qualifying 

PVCP-PIPs pose low risk with respect to 

concerns associated with protein 

production. Therefore, EPA is proposing 

that, under § 174.27(c)(2), a PVCP-PIP 

would also meet § 174.27(c) if: 

The Agency determines after review that 

the genetic material that encodes the 

pesticidal substance or leads to the 

production of the pesticidal substance: 

(i) Encodes a protein that is minimally 

modified from a coat protein from a virus 

that naturally infects plants, or 

(ii) Produces no protein. 

EPA developed the criterion in 

§ 174.27(c)(2) because the Agency 

recognizes that developers may wish to 

modify PVCP-PIP constructs to achieve 

certain product development goals such 

as greater efficacy, and such 

modifications might result in changes to 

the protein(s) produced. Most minor 

modifications to the genetic material 

would be unlikely to cause changes to 

the protein that would be significant 

from a human or nontarget organism 

perspective. Under § 174.27(c)(2) EPA 

may consider such modifications on a 

case-by-case basis. Many of the 

modifications are likely to produce 

proteins that fall within the range of 

natural variation of the virus. However, 

it is not currently possible to define 

clearly the range of variation of viruses 

in general or even of any particular 

virus as discussed in Unit IV.D. of the 

companion document published in 

today’s Federal Register. Therefore, 

§ 174.27(c)(2)(i) requires an Agency 

review to determine qualification. 

PVCP-PIPs are known to confer 

resistance by two mechanisms. 

Resistance may be either proteinmediated, in which the level of 

resistance is correlated with the level of 

protein expression, or it may be RNAmediated, in which the level of 

resistance is not correlated with the 

level of protein expression. (See 

discussion in Unit II.E.) In the case of 

RNA-mediated resistance, little to no 

PVC-protein may be produced from the 

PVCP-PIP. In such cases, little to no risk 

due to protein production would be 

associated with the PVCP-PIP. However, 

the Agency believes that the only 

conditions that can a priori indicate 

there will be no protein production are 

encompassed by the criterion in 

§ 174.27(c)(1). Any other type of 

construct that may confer RNAmediated resistance through PTGS 

would be reviewed by the Agency under 

the criterion in § 174.27(c)(2)(ii). A 

PVCP-PIP would meet § 174.27(c) if EPA 

determines that no PVC-protein is 

produced from the PVCP-PIP. 

If protein is produced, today’s 

proposed exemption would cover only 

those PVC-proteins that are not 

significantly different from naturally 

occurring plant viral coat proteins, i.e., 

proteins that are virtually unmodified or 

minimally modified. For more 

significantly modified PVC-proteins, the 

base of experience upon which EPA 

relies for support of the proposed 

exemption would not be applicable. 

Therefore, EPA would not be able to 

make the determination a priori as part 

of this proposed rule that the PVCP-PIP 

poses a low probability of risk to 

humans and the environment and will 

not generally cause unreasonable 

adverse effects on the environment even 

in the absence of regulatory oversight 

under FIFRA. However, such PVCP-PIPs 

may still be eligible for registration, and 

any significantly modified PVC-proteins 

could be evaluated as part of the 

registration review (as discussed in Unit 

II.G.). (For discussion of the concept of 

‘‘minimally modified’’ see Unit IV.E.2. 

of the companion proposed exemption 

published in today’s Federal Register.) 

3. Historical approaches. EPA’s 

current proposed approach is consistent 

with what EPA has always intended. 

EPA has never intended that any 

proposed exemption for PVCP-PIPs 

would cover those PIPs that produce 

proteins significantly different from 

those that occur naturally (November 

23, 1994, 59 FR at 60524; July 19, 2001, 

66 FR 37865 and 66 FR 37796). 

IV. Proposed Exemption for Certain 

Inert Ingredients 

As noted in Unit II.F. of this 

preamble, one of the general 

qualifications for exemption at § 174.21 

is that ‘‘any inert ingredient that is part 

of the plant-incorporated protectant is 

on the list codified at §§ 174.485 

through 174.490.’’ EPA is proposing to 

add several substances to § 174.486 

when they are used in a PIP that is listed 

in 40 CFR part 174 subpart B - 

Exemptions and are in a plant that 

satisfies § 174.27(a): 

• beta-D-glucuronidase (GUS) from 

Escherichia coli and the genetic material 

necessary for its production, 

• neomycin phosphotransferase II 

(NPTII) and the genetic material 

necessary for its production, 

• phosphomannose isomerase (PMI) 

and the genetic material necessary for 

its production, 

• CP4 enolpyruvylshikimate-3- 

phosphate (CP4 EPSPS) and the genetic 

material necessary for its production, 

• glyphosate oxidoreductase (GOX or 

GOXv247) and the genetic material 

necessary for its production, and 

• phosphinothricin acetyltransferase 

(PAT) and the genetic material 

necessary for its production. 

Below is a summary of EPA’s finding 

that these inert ingredients present a 

low risk to human health and the 

environment; the docket for this 

proposed rule contains the Agency’s full 

risk assessment in the document 

‘‘Environmental Risk Assessment of 

Plant-Incorporated Protectant (PIP) Inert 

Ingredients.’’ EPA also proposes to add 

to subpart X the partial tetracycline 

resistance gene as present under the 

control of a bacterial promoter in 

papaya line 55–1. 

EPA has conducted an environmental 

risk assessment of the PIP inert 

ingredient phosphinothricin 

acetyltransferase (PAT) and the genetic 

material necessary for its production. 

Topics covered in this assessment 

include mode of action, ecological 

effects, endangered species 

considerations, and gene flow from a 

modified plant to wild or weedy 

relatives. Data cited in this assessment 

were submitted to the Agency in 

support of Dekalb’s DBT 418 and Ciba 

Seed’s Event 176 Bt corn registrations 

and Syngenta’s COT 102 Bt cotton 

registration. Ecological data and 

published information on the biology of 

this protein indicate that this PIP inert 

ingredient is not known to be toxic and/ 

or pathogenic to plant or animal species. 

In 1997, the Agency granted a tolerance 

exemption for this PIP inert ingredient 

in all plants due to the low human 

health risks associated with this protein 

(40 CFR 180.1151; 62 FR 17717, April 

11, 1997). Based on all of its 

assessments, EPA has determined that 

this inert ingredient will pose low 

ecological and occupational risk. 

EPA has conducted an environmental 

risk assessment of the PIP inert 

ingredient CP4 enolpyruvylshikimate-3- 

phosphate synthase (CP4 EPSPS) and 

the genetic material necessary for its 

production. Topics covered in this 

assessment include mode of action, 

ecological effects, endangered species 

considerations, and gene flow from a 

modified crop to wild or weedy 

relatives. Data cited in this assessment 

were submitted to the Agency in 


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support of Monsanto’s MON 810 Bt 

Corn registration. Ecological data and 

published information on the biology of 

this protein indicate that this PIP inert 

ingredient is not known to be toxic and/ 

or pathogenic to plant or animal species. 

In 1996, the Agency granted a tolerance 

exemption for this PIP inert ingredient 

in all plants due to the low human 

health risks associated with this protein 

(40 CFR 180.1174; 61 FR 40338, August 

2, 1996). Based on all of its assessments, 

EPA has determined that this inert 

ingredient will pose low ecological and 

occupational risk. 

EPA has conducted an environmental 

risk assessment of the PIP inert 

ingredient glyphosate oxidoreductase 

(GOX) and the genetic material 

necessary for its production. Topics 

covered in this assessment include 

mode of action, ecological effects, 

endangered species considerations, and 

gene flow from a modified crop to wild 

or weedy relatives. Data cited in this 

assessment were submitted to the 

Agency in support of Monsanto’s MON 

810 Bt Corn registration. Ecological data 

and published information on the 

biology of this protein indicate that this 

PIP inert ingredient is not known to be 

toxic and/or pathogenic to plant or 

animal species. In 1997, the Agency 

granted a tolerance exemption for this 

PIP inert ingredient in all plants due to 

the low human health risks associated 

with this protein (40 CFR 180.1190; 62 

FR 52505, October 8, 1997). Based on all 

of its assessments, EPA has determined 

that this inert ingredient will pose low 

ecological and occupational risk. 

EPA has conducted an environmental 

risk assessment of the PIP inert 

ingredient neomycin 

phosphotransferase II (NPTII) and the 

genetic material necessary for its 

production. Topics covered in this 

assessment include mode of action, 

ecological effects, endangered species 

considerations, and gene flow from a 

modified crop to wild or weedy 

relatives. Data cited in this assessment 

were submitted to the Agency in 

support of Monsanto’s NewLeaf Potato 

and YieldGard Plus Corn registrations 

and is discussed in more detail in the 

Bacillus thuringiensis PlantIncorporated Protectant and MON 863 

Biopesticide Registration Action 

Documents (Ref. 123). Ecological data 

and published information on the 

biology of this protein indicate that this 

PIP inert ingredient is not known to be 

toxic and/or pathogenic to plant or 

animal species. In 1994, the Agency 

granted a tolerance exemption for this 

PIP inert ingredient in all plants due to 

the low human health risks associated 

with this protein (40 CFR 180.1134; 59 

FR 49351, September 28, 1994). Based 

on all of its assessments, EPA has 

determined that this inert ingredient 

will pose low ecological and 

occupational risk. 

EPA has conducted an environmental 

risk assessment of the Escherichia coliderived PIP inert ingredient beta-Dglucuronidase (GUS) and the genetic 

material necessary for its production. 

Topics covered in this assessment 

include mode of action, ecological 

effects, endangered species 

considerations, and gene flow from a 

modified crop to wild or weedy 

relatives. Data cited in this assessment 

were submitted to the Agency in 

support of Monsanto’s Bollgard II Bt 

cotton registration and are discussed in 

the Bollgard II Biopesticide Registration 

Action Document (Ref. 124). Ecological 

data and published information on the 

biology of this protein indicate that this 

PIP inert ingredient is not known to be 

toxic and/or pathogenic to plant or 

animal species. In 2001, the Agency 

granted a tolerance exemption for this 

PIP inert ingredient in all plants due to 

the low human health risks associated 

with this protein (40 CFR 180.1216; 66 

FR 42957, August 16, 2001). Based on 

all of its assessments, EPA has 

determined that this inert ingredient 

will pose low ecological and 

occupational risk. 

EPA has conducted an environmental 

risk assessment of the Escherichia coliderived PIP inert ingredient 

phosphomannose isomerase (PMI) and 

the genetic material necessary for its 

production. Topics covered in this 

assessment include mode of action, 

ecological effects, endangered species 

considerations, and gene flow from a 

modified crop to wild or weedy 

relatives. Data cited in this assessment 

were submitted to the Agency in 

support of Syngenta’s MIR604 Bt corn 

registration. Ecological data and 

published information on the biology of 

this protein indicate that this PIP inert 

ingredient is not known to be toxic and/ 

or pathogenic to plant or animal species. 

In 2004, the Agency granted a tolerance 

exemption for this PIP inert ingredient 

in all plants due to the low human 

health risks associated with this protein 

(40 CFR 180.1252; 69 FR 26770, May 14, 

2004). Based on all of its assessments, 

EPA has determined that this inert 

ingredient will pose low ecological and 

occupational risk. 

EPA believes the partial tetracycline 

resistance gene as present in papaya line 

55–1 presents low risk to human health 

and the environment and could also be 

added to 40 CFR part 174 subpart X. No 

protein is expected to be produced from 

the gene because it is under the control 

of a prokaryotic promoter and is only a 

partial gene that is not expected to 

function in plants (Ref. 125). Therefore, 

no ecological or human health effects 

would be associated with this inert 

ingredient as found in papaya line 55–

1 because it consists of only DNA. 

Transfer of an antibiotic resistance 

marker gene from plants to 

microorganisms in the gut or in the 

environment may theoretically be 

possible, but it is extremely unlikely 

(Refs. 126 and 127). In addition, because 

only a portion of the tetracycline 

resistance gene is present in papaya line 

55–1, if any horizontal gene transfer of 

this genetic material were to occur, it 

would be unlikely to confer antibiotic 

resistance to any organism that acquired 

it (Ref. 125). 

EPA asked the 2005 SAP to comment 

on the Agency’s environmental risk 

assessment for the first six of these 

selectable markers. The Panel 

concluded that the ‘‘antibiotic resistance 

marker (NPTII) and other markers (GUS 

and PMI) should be exempt provided 

they were in the plant species 

determined to be of low risk using 

criteria’’ the SAP proposed as discussed 

in Unit III.C.2.i. (Ref. 11) and EPA relied 

on, as appropriate, in developing the list 

comprising § 174.27(a)(1). In addition, 

the Panel concluded that the ‘‘herbicide 

markers (CP4 EPSPS, GOX/GOXv247 

and PAT) should not be exempted, but 

rather should be considered on a caseby-case basis taking into consideration 

the potential that the crop plant has to 

become feral’’ (Ref. 11). EPA notes, 

however, that the only crop plants that 

will be included on the list comprising 

§ 174.27(a)(1) are those whose potential 

to become feral has been considered. 

Thus, EPA’s inclusion of these six 

selectable markers in 40 CFR part 174 

subpart X - List of Approved Inert 

Ingredients when they are used in PIPs 

as inert ingredients in a plant that 

satisfies § 174.27(a) is consistent with 

the 2005 SAP’s recommendations 

regarding these inert ingredients. 

EPA is also considering an alternative 

under which NPTII, GUS, and PMI 

would be exempt from FIFRA when 

used as inert ingredients with any 

exempt PIP, regardless of the plant in 

which they are expressed. Although the 

SAP recommended that they only be 

exempt provided they were used in a 

plant species determined to be of low 

risk based on the considerations 

encompassed in § 174.27(a), the Panel 

did not provide a rationale as to why the 

markers would not be considered low 

risk in other plants as well. Given that 

these markers are widespread in the 

environment and would be expected to 

confer no particular selective advantage 


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on any plant in the environment that 

might express them, the Agency knows 

of no rationale why this limitation 

would be necessary. The Agency 

believes that its risk assessment would 

support such an exemption for these 

inert ingredients. 

EPA is also proposing a technical 

correction to § 174.480 to make the 

language consistent with the general 

requirements for exemption, which 

recognize that for some PIPs no FFDCA 

tolerance may be required. In such 

cases, it is not necessary that the inert 

ingredients have been exempted from 

FFDCA section 408 requirements. 

V. Economic Analysis 

Virus infection is a serious problem in 

agricultural production. Virtually every 

plant species is susceptible to infection 

by at least one of more than 500 known 

plant viruses (Ref. 6). Particular crop or 

weed hosts are nearly always infected 

by certain plant viruses under natural 

conditions (Ref. 103). Plant viruses 

create economic losses for a vast variety 

of crops by reducing yields and 

negatively affecting the quality of the 

crop, damaging fruits, leaves, seeds, 

flowers, stems, and/or roots (Refs. 103 

and 128). Symptom development and 

vector transmission rates are affected by 

the environment and so can vary across 

locations or seasons (Ref. 103). 

Virus diseases have often resulted in 

devastating agricultural losses, at times 

destroying entire plantings of crops in 

certain locations (Ref. 103). For 

example, more than 100 million citrus 

trees had been destroyed by citrus 

tristeza virus (CTV) by 1991 in citrus 

growing regions around the world, 

including California (Ref. 129). CTV is 

one of the most economically important 

viruses because of its widespread 

distribution, the severity of damage 

caused by infection, and the long life 

span of individual trees (Ref. 130). 

Growers may need to use several 

control methods during a crop season in 

an attempt to prevent viral infection and 

dissemination, primarily by planting 

virus-free material for mechanically 

transmitted viruses. For vectortransmitted viruses, control measures 

have often focused on chemical 

insecticides, fungicides, and 

nematicides to reduce the population of 

vectors that transmit viruses from plant 

to plant. However, control of vectors is 

not always feasible or effective as a way 

to control virus transmission (Ref. 103). 

In another common control strategy, 

crops are grown in rotation with crops 

that the virus does not infect to reduce 

the virus load in the field. This method 

has serious limitations as well. In some 

cases, the development of resistant 

cultivars can be the only viable means 

of virus control. Plants developed 

through conventional breeding 

techniques offer some degree of virus 

resistance. However, breeding for 

resistance has not been successful for 

the majority of field crops that are 

severely affected by viruses (Ref. 128). 

In some agricultural regions, some crop 

species cannot be grown effectively 

because of the persistent presence of 

infected plant populations and/or 

potential virus vectors (Ref. 103). 

Contrary to traditional control measures, 

transgenic virus-resistant crops offer an 

effective means of virus protection. 

This proposed rule would benefit the 

public by ensuring protection of human 

health and the environment while also 

reducing the cost of and time needed for 

regulatory review of transgenic virusresistant crops. This proposal would 

also help to appropriately allocate 

Federal resources for risk evaluation by 

focusing Agency attention on those 

PVCP-PIPs that warrant review. This 

proposed rule would also benefit the 

industry by removing regulatory 

uncertainty for this class of products. 

This economic analysis (EA) prepared 

for this proposed rule estimates the 

projected compliance cost for the 

industry under the baseline of full 

registration for all PVCP-PIPs and 

compares that to the compliance cost for 

the potentially affected industry under 

the proposed rule in order to estimate 

the expected savings from the regulation 

relief. The steps used to obtain a cost 

estimate for the proposed rule are 

summarized below. 

Since the nature and timing of future 

development of PVCP-PIPs are 

unknown, the EA begins by identifying 

nine case studies that represent the 

broadest range of PVCP-PIPs that the 

Agency anticipates could be developed 

in the future. After considering the 

characteristics of the products that have 

already been marketed, characteristics 

of the crop plants that have been the 

subject of field trials for PVCP-PIPs, and 

knowledge of the field of genetically 

engineered virus-resistant crops, EPA 

estimated the percentage of products 

projected to be characterized by each 

case study, i.e., the ‘‘prevalence’’ of the 

case study. The stated prevalence 

represents the best estimate of the 

expectation of a PVCP-PIP product like 

the one in a specific case study being 

developed in the future. 

For each case study, a set of data 

would be required of a developer in 

order to register the PVCP-PIP. The cost 

and burden of potential data 

requirements for each case study under 

the baseline are compared with the 

potential data requirement costs and 

burden under the proposed option. 

Using the prevalence for each case 

study, EPA estimated the probability of 

developing a PVCP-PIP product like that 

examined in any of the case studies in 

any year, given that the Agency 

anticipates 1.5–2.5 PVCP-PIPs being 

developed each year over a 10–year 

period. These probabilities determine 

the frequency and timing of 

development and registration of PVCPPIPs in a model EPA designed to 

compute compliance cost savings. 

To estimate compliance cost savings 

in any year, the number of PVCP-PIPs 

like the one developed in a given case 

study was multiplied by the difference 

between cost and burden under the 

proposed rule and baseline. Since the 

model made use of probabilities, the 

average of 5,000 simulations was 

computed for each year to represent the 

annual compliance cost savings for the 

proposed rule. Using this procedure, the 

estimated annual impact, based on 

average cost estimates per data 

requirement, is expected to result in a 

regulatory compliance cost reduction 

approximately within the range of 

$340,000 and $360,000 a year. Over a 

10–year period, the annual average 

regulatory compliance cost reduction is 

expected to be approximately $350,000. 

The potential exemptions under the 

proposed rule, as compared to the 

baseline under which no PVCP-PIPs are 

exempted, would reduce regulatory 

costs for the potentially affected 

industry and the EPA, remove 

regulatory uncertainty for industry, and 

provide important information to the 

public regarding the safety of exempted 

PVCP-PIPs. Entities that may benefit 

from the proposed rule and alternative 

options are the public, companies that 

develop and market PVCP-PIPs 

(applicants and/or registrants), farmers, 

and the environment. However, 

potential future benefits to these entities 

are difficult to quantify due to data 

limitations and uncertain market 

conditions. In addition, considerable 

difficulty exists in quantitatively 

evaluating non-market benefits, such as 

reduced environmental and human 

health risks, consistency of regulation, 

reduced regulatory uncertainty, and 

improvements in public perception of 

biotechnology products. 

VI. Preliminary Statutory Finding 

A. What Risk Assessment Methodology 

did EPA use for this Proposed Rule? 

Generally, when EPA assesses the 

risks caused by the use of a pesticide, 

it considers both the potential hazard 

that the pesticide poses to the 

environment and the potential for 


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exposure to the pesticide due to its use. 

For most pesticides (e.g., chemical 

pesticides), EPA relies on data generated 

by laboratory testing using 

representative animal models to 

estimate hazard endpoints. To develop 

exposure estimates the Agency 

evaluates other information including 

product characterization data, proposed 

use patterns, and information generated 

from mathematical models. Exposure 

and hazard estimates are combined to 

quantify the potential risk associated 

with the pesticide’s use. The data 

requirements describing the types of 

information to be generated and other 

guidance for assessing risk are detailed 

in 40 CFR part 158. 

The questions posed as part of the risk 

assessment in evaluating most 

pesticides (e.g., biological or chemical 

pesticides) can also be posed for the 

PVCP-PIPs that are exempted in this 

proposed action, and 40 CFR part 158 

can be used as guidance. EPA adopted 

an approach for evaluating the potential 

risks of PVCP-PIPs that is consistent 

with the unique characteristics of 

pesticides produced and used in a living 

plant and the scientific knowledge and 

experience accumulated on these 

substances. 

To address the hazard endpoints 

described in 40 CFR part 158 for the 

PVCP-PIPs that qualify for this proposed 

exemption, EPA relied on a very large 

body of information in the public 

literature that was developed through 

many decades of testing and 

observation. EPA thus did not need to 

rely on animal model testing for 

assessing risk as it would for most other 

pesticides (e.g., chemical pesticides) 

where specific hazard data are lacking. 

In addition, PIPs are produced within 

the living plant, and the pesticidal 

substance is used in situ in the plant. 

Exposure to PVCP-PIPs is therefore 

limited relative to exposure to chemical 

pesticides that are applied broadly in 

the environment, e.g., through aerial 

application. 

1. Large body of knowledge and 

experience exists. Typically, in 

assessing a pesticide for environmental 

risk, EPA considers data fulfilling the 

information requirements posed in 40 

CFR part 158 to evaluate the potential 

effect of the pesticide on birds, 

mammals, freshwater fish and 

invertebrates, estuarine and marine 

animals, and nontarget plants and 

insects (e.g., predators, parasites, and 

pollinators). For most pesticides, this 

information must be generated using 

animal models. To address these same 

questions for the PVCP-PIPs that are the 

subject of this proposed exemption, EPA 

was able to rely on a long history of 

hundreds, if not thousands of years of 

natural exposure to plant virus coat 

proteins by nontarget organisms. EPA 

relies on these experiences and the 

scientific literature generated by a 

century of food safety studies (Refs. 131 

and 132) to assess the PVCP-PIPs that 

are the subject of these exemptions. 

EPA also took into account the large 

and varied information base available in 

the public scientific literature from a 

number of disciplines including plant 

genetics, plant physiology, plant 

virology, weed science, molecular 

biology, biochemistry, ecology, and 

plant breeding. For example, the Agency 

used experimental data derived from the 

science of plant pathology to 

characterize the pest resistance 

mechanisms in plants (Ref. 56) and 

relied on the scientific knowledge base 

of plant virology and virus ecology to 

evaluate how plant viruses interact with 

each other and with the plant during 

infection (Ref. 60). 

2. PVCP-PIPs are produced within the 

living plant, and the pesticidal 

substance is used in situ in the plant, 

affecting the exposure paradigm. EPA 

used information from the fields of 

plant pathology, biochemistry, 

microbial ecology, and ecology in 

considering all aspects of risk, including 

exposure. PVCP-PIPs are produced 

within the living plant itself, and the 

pesticidal substance is used in situ in 

the plant to protect against pests, in 

contrast to most other pesticides, which 

must be applied to or near the plant. 

Because a PVCP-PIP is produced and 

used within the plant, physiological 

constraints limit the amount of 

pesticidal substance produced by the 

plant. Regardless of the tissues 

containing the PVCP-PIP or the level at 

which PVC-protein is expressed, the 

PVCP-PIP, including any PVC-protein, 

is contained within the plant parts. 

Therefore, the routes by which other 

organisms may be exposed to the PVCPPIP may be more limited, e.g., dietary 

exposure is likely to be the predominant 

route of exposure, and physical contact 

with the plant or plant parts will 

generally be necessary for exposure to 

occur. 

The PVCP-PIPs exempted by this 

proposed rule are biotic and are subject 

to the processes of biodegradation and 

decay that all such materials undergo 

(Ref. 133). Biotic materials are broken 

down to constituent parts through the 

enzymatic processes of living 

organisms, and these constituent parts 

are used as building blocks during 

growth of other biotic substances. In 

addition, PVCP-PIPs are biodegradable 

to their constituent elements through 

catabolism by living organisms. Because 

of their biodegradable nature, PVCPPIPs do not bioaccumulate (i.e., build 

up in tissues because the body is unable 

to either break the substance down or 

eliminate it) or biomagnify (i.e., 

progressively build up in successive 

trophic levels because it bioaccumulates 

in the bodies of organisms lower in the 

food chain). Because of these 

characteristics, the potential for new 

exposures to occur beyond direct 

physical exposures to the plant or plant 

parts is limited. 

A question directly affecting the 

exposure component of the risk 

assessment that has no equivalent in the 

assessment of more traditional 

pesticides (e.g., chemical pesticides) 

must be posed for PIPs. Because PIPs are 

produced and used in the living plant, 

the possibility that the ability to 

produce a PIP may be transferred by 

outcrossing and hybridization from the 

crop plant to a wild or weedy relative 

was considered. A large volume of 

information is available in the public 

literature to assess the risks of gene flow 

generally (Refs. 19 and 134) and for 

PVCP-PIPs in particular (Refs. 12, 32, 

36, 135, 136, 137, 138, 139, and 140). 

B. Exemption Determination for PVCPPIPs, Including Certain Inert Ingredients 

EPA preliminarily concludes that 

PVCP-PIPs that meet the criteria 

specified in this proposed action 

warrant exemption under FIFRA section 

25(b)(2). The use of PVCP-PIPs that meet 

the criteria in 40 CFR 174.21, including 

the criteria proposed in this Federal 

Register to be inserted at 40 CFR 174.27 

poses a low probability of risk to the 

environment and is not likely to cause 

unreasonable adverse effects in the 

absence of regulatory oversight. EPA 

bases this preliminary conclusion upon 

an evaluation of the potential risks that 

use of PVCP-PIPs qualifying for this 

exemption would reasonably pose to 

man and the environment, and upon an 

evaluation of whether their use causes 

unreasonable adverse effects. EPA 

preliminarily concludes that PVCP-PIPs 

qualifying for this exemption pose a low 

probability of risk to the environment as 

demonstrated by information from the 

fields of plant genetics, plant 

physiology, plant virology, weed 

science, molecular biology, 

biochemistry, ecology, and plant 

breeding; from many years of experience 

growing and consuming plants that 

contain coat proteins from plant viruses; 

and from Agency knowledge about 

horticultural and agricultural practices. 

EPA also believes that use of these 

plant-incorporated protectants in food is 

safe under the FFDCA section 408 

standard as explained in the preamble 


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to this document and the companion 

document published elsewhere in this 

issue of the Federal Register exempting 

residues of the PVC-protein portion of a 

PVCP-PIP. 

EPA believes that PVCP-PIPs that 

meet the criteria in 40 CFR 174.21, 

including the criteria proposed in this 

Federal Register to be added at 40 CFR 

§ 174.27, are also not likely to cause 

unreasonable adverse effects, even in 

the absence of regulatory oversight. As 

a result, EPA concludes that PVCP-PIPs 

qualifying for this exemption do not 

cause any unreasonable adverse effects 

with respect to human dietary risk. 

Taking into account the economic, 

social, and environmental costs and 

benefits of the use of such products, as 

discussed in the preamble and 

associated Economic Analysis (found in 

the docket for this rulemaking), EPA 

believes that the low levels of risks that 

such products present do not justify the 

cost of regulating such products. Note 

that products that qualify for this 

exemption would remain subject to the 

requirement for submission of 

information regarding adverse effects 

under 40 CFR 174.71. Even though EPA 

believes the probability is very low that 

risks would arise with the PVCP-PIPs 

qualifying for this exemption, the 

adverse effects reporting requirement 

will alert the Agency should any such 

rare circumstances occur. EPA could 

then address such instances, as 

appropriate, under FIFRA. 

VII. Request for Comment 

EPA requests comment on whether 

the Agency has appropriately identified 

in this proposed exemption those PVCPPIPs that are of a nature not requiring 

regulation under FIFRA. In particular, 

the Agency requests comment on the 

following specific issues: 

1. EPA requests comment on whether 

additional plants could be appropriately 

included in the list of plants comprising 

proposed § 174.27(a)(1) because they 

would present low risk with respect to 

concerns associated with weediness of 

the plant itself and any wild or weedy 

relatives of the plant if it were to 

contain any PVCP-PIP. For example, the 

2004 SAP identified the following 

plants that are not included in proposed 

§ 174.27(a)(1): almond (Prunus 

communis), apricot (Prunus armeniaca), 

cape daisy (Osteospermum spp.), 

chrysanthemum (Dendranthema spp.), 

celery (Apium graveolens), eggplant 

(Solanum melongena), geranium 

(Pelargonium spp.), hyacinth 

(Hyacinthus spp.), guava (Psidium 

guajava), kiwi (Actinidia spp.), 

nectarine and peach (Prunus persica), 

okra (Abelmoschus esculentus), olive 

(Olea europaea), parsley (Petroselinum 

crispum), petunia (Petunia spp.), 

pistachio (Pistacia vera), plum (Prunus 

domestica), spinach (Spinacia oleracea), 

taro (Colocasia esculenta), tomato 

(Solanum lycopersicum), watermelon 

(Citrullus lanatus), and wishbone flower 

(Torenia spp.). 

EPA would be particularly interested 

in information about these plants or 

others that addresses the questions in 

Unit III.C.2.i. that EPA posed to crop 

experts as part of its evaluation as to 

whether specific species should be 

included on the list. In some cases, EPA 

has already consulted with one or more 

experts for these plants, but the Agency 

does not believe it has the information 

necessary to draw a conclusion for these 

plants. Given the reliance on expert 

opinion to make these determinations, 

EPA would like to have responses from 

at least three experts for any given crop 

before including it on the list at 

§ 174.27(a)(1). In other cases, EPA 

completed at least three consultations, 

but the Agency received information 

from at least one expert suggesting that 

the plant may not meet the low risk 

standard for inclusion in the 

§ 174.27(a)(1) list, e.g., because of 

questions about the formation of viable 

hybrids in nature with wild or weedy 

relatives or questions about the 

propensity of the crop to naturalize. 

EPA describes its analyses in the 

following paragraphs and requests 

assistance from the public on the issues 

raised. 

EPA is inclined to include almond 

(Prunus communis) on the list in 

§ 174.27(a)(1) on the basis of 

information received from expert 

consultations. However, EPA is seeking 

any information from the public that 

would enable the Agency to complete 

its assessment of the potential for a 

PVCP-PIP to introgress into a population 

of a wild or weedy relative or a 

naturalized population of the species 

and what effect such introgression 

might have. Specifically, the experts 

indicated that natural hybrids may be 

able to form with some other stone fruit 

trees (Ref. 42). However, if such trees 

are likely to be found in commercial 

cultivation, natural hybrids would not 

necessarily be expected in areas outside 

of managed orchards. Regarding 

whether almond is a weedy species, 

both experts mentioned that almond 

forms feral populations. However, they 

have not usually required weed 

management activity because ‘‘the trees 

are infrequent and tend to be seen as 

beneficial’’ (Ref. 42). One expert said, 

‘‘Almond is not highly susceptible to 

viruses affecting other Prunus tree crop 

species. Thus virus resistance is not a 

major determinate of feral almond 

fitness in current environments.... Thus, 

it is likely that transgenic resistance 

would not greatly benefit either 

commercial or feral almonds’’ (Ref. 42). 

EPA is inclined to include amaryllis 

(Hippeastrum spp.) on the list in 

§ 174.27(a)(1) on the basis of 

information received from consultations 

with amaryllis experts that EPA 

conducted upon recommendation from 

other experts in flower breeding. 

However, EPA is seeking any 

information from the public that would 

enable the Agency to complete its 

assessment of the weedy characteristics 

of amaryllis and the potential for gene 

exchange between feral and cultivated 

populations. Two experts indicated that 

there are no wild or weedy relatives in 

the United States with which amaryllis 

can form viable hybrids in nature, 

although one expert said, ‘‘Hippeastrum 

puniceum (Lam.) Kuntze is naturalized 

in Puerto Rico, the Virgin Islands, 

Louisiana and Hawaii. Hippeastrum 

puniceum is a diploid species that is 

occasionally used in breeding programs. 

In controlled crosses, it will breed with 

other diploid species, and is probably 

represented in modern Hippeastrum 

cultivars. However, most modern 

Hippeastrum cultivars available in the 

florist and greenhouse trade are 

complex, tetraploid hybrids that are 

difficult to backcross to H. puniceum’’

(Ref. 42). One expert believed that no 

species in the genus are known to 

become feral or easily spread into noncrop areas. However, the others noted 

that this occasionally occurs without 

requiring weed management activity. 

One said, ‘‘Hippeastrum puniceum may 

have been introduced into Puerto Rico, 

possibly during pre-Colombian times, 

and it has since sparingly naturalized.... 

Spread is slow and minimal and has not 

required management activity’’ (Ref. 42). 

Another said, ‘‘Plants generally 

naturalize in disturbed areas along 

roadsides and irrigation ditches. The 

species is self-incompatible, but can 

form seed in naturalized settings. The 

plants also reproduce asexually via offsets. Long distance dispersal appears 

minimal. Hippeastrum puniceum is 

considered a low-risk introduced plant 

in Hawaii and appears that it does not 

require active weed-management’’ (Ref. 

42). All three experts agreed that it was 

unlikely acquisition of virus resistance 

would cause amaryllis to become feral 

or easily spread into non-crop areas in 

the United States. For example, one 

expert said, ‘‘Hippeastrum has been 

grown commercial outdoors since the 

early 1900’s in semi-tropical areas of the 

US (Hippeastrum is not winter-hardy). 


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There has not been a single record of 

any plants escaping and becoming feral. 

There is no reason to believe that 

acquiring transgenic resistance to one or 

more viruses would increase the ability 

of plants to become feral or easily 

spread into non-crop areas’’ (Ref. 42). 

EPA is inclined to include apricot 

(Prunus armeniaca) on the list in 

§ 174.27(a)(1) on the basis of 

information received from expert 

consultations. However, EPA is seeking 

any information from the public that 

would enable the Agency to complete 

its assessment of the potential for a 

PVCP-PIP to introgress into a population 

of a wild or weedy relative or a 

naturalized population of the species. 

Specifically, two experts indicated that 

apricot may be able to cross with plum 

species because ‘‘[i]f planted in close 

proximity apricot can be crossed by bees 

to Japanese plums. That suggests the 

same could happen with native US 

plum species, of which there are many 

in the eastern US’’ (Ref. 42). However, 

both experts suggested that the 

frequency of hybrid production would 

be extremely low. Two experts 

indicated that apricot is not known to 

become feral or easily spread into noncrop areas, while the third expert said 

that he has ‘‘seen rare plants in 

[Michigan] that are feral or left-over 

homeowner trees. They did not appear 

to spread as the big seeds mostly drop 

under the trees and seem not very 

competitive compared to the weeds’’

(Ref. 42). All of the experts agreed that 

acquisition of virus resistance would be 

unlikely to change apricot’s propensity 

to become feral. According to one 

expert, ‘‘It is not likely that this would 

occur because climatic conditions and 

the occurrence of fungal and bacterial 

diseases are more limiting than the 

viruses’’ (Ref. 42). 

EPA believes that more information 

about cape daisy (Osteospermum spp.) 

is needed to address issues raised by 

expert consultation. EPA is seeking any 

information from the public that would 

enable the Agency to complete its 

assessment of the potential for a PVCPPIP to enhance the potential of species 

in this genus to naturalize. One expert 

indicated, ‘‘Osteospermum fruticosum 

is a low-risk naturalized plant in 

Hawaii, and is also found, along with O. 

ecklonis, in California. Other 

Osteospermum species have naturalized 

in Australia and New Zealand. The 

genus is endemic to the Cape Floristic 

Region of southern Africa which has a 

Mediterranean climate. Thus, there is 

potential for more species of 

Osteospermum to naturalize in 

California which, like Australia and 

New Zealand, has a Mediterranean 

climate.... Transgenic or not, 

Osteosperum [sic] has potential to 

further naturalize in Mediterranean 

climates and needs further monitoring 

for invasive potential in these areas’’

(Ref. 42). However, the other two 

experts indicated that it was unlikely 

that virus resistance would cause cape 

daisy to become feral or easily spread 

into non-crop areas. One said, ‘‘Other 

factors are much more likely to limit its 

invasive potential, such as available 

moisture, presence of competing 

vegetation, and predation by insects and 

vertebrates. Viruses do not appear to be 

limiting its spread’’ (Ref. 42). The other 

expert said, ‘‘Viral resistance could 

conceivably increase fecundity and 

spread, but there is no data to confirm 

or refute the possibility’’ (Ref. 42). 

EPA is inclined to include 

chrysanthemum (Dendranthema spp.) 

on the list in § 174.27(a)(1) on the basis 

of information received from 

consultations with two chrysanthemum 

experts. These experts indicated that 

there are no wild or weedy relatives in 

the United States with which 

commercial chrysanthemum can form 

viable hybrids in nature. One expert 

believed that no species in the genus are 

known to become feral or easily spread 

into non-crop areas, while the other 

noted that this has occurred rarely in 

California, Ohio, Pennsylvania, and 

Massachusetts. Nevertheless, these 

populations have not required weed 

management activity because they 

‘‘have remained small consisting of only 

a few plants’’ (Ref. 42). Both experts 

believed it unlikely that acquired virus 

resistance could lead to commercial 

chrysanthemum becoming feral or easily 

spreading into non-crop areas. One 

expert said, ‘‘Plants in the genus 

Dendranthema are generally not easily 

propagated by seed, and are vegatatively 

[sic] propagated by cuttings or division. 

They do not compete well with other 

plants and do not persist in untended 

garden situations, and would certainly 

not do so in non-crop areas’’ (Ref. 42). 

EPA has received one response from 

an eggplant expert suggesting that 

eggplant (Solanum melongena) meets 

the requirements for inclusion on the 

list in § 174.27(a)(1). This consultation 

indicates that eggplant meets the three 

conditions outlined above by the SAP: 

it does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make eggplant weedy 

or invasive. The expert said, ‘‘Similar to 

other species where wild relatives have 

been utilized to enhance the cultivated 

form of the crop, genes for improved 

fitness are derived from the wild 

relative. Neither the disease resistant 

wild relative nor the improved cultivars 

have shown a propensity to become 

feral’’ (Ref. 42). EPA is seeking public 

comment on this determination because 

the Agency desires a more robust 

response base. 

EPA believes that more information 

about geranium (Pelargonium spp.) is 

needed to address issues raised by 

expert consultation. EPA is seeking any 

information from the public that would 

enable the Agency to complete its 

assessment of the potential for a PVCPPIP to spread to a wild or weedy 

population in the United States or 

enhance the potential of species in this 

genus to naturalize. Regarding the 

potential for spread to a wild or weedy 

population, two experts indicated that 

species within this genus do not form 

viable hybrids in nature with wild or 

weedy relatives in the United States, but 

a third expert said, ‘‘In the wild, P. 

cucullatum will hybridize with P. 

betulinum (L.) L’Her. and P. patulum 

Jacq. Pelargonium grandiflorum forms 

natural hybrids with P. sublignosum 

Knuth. The extent to which these 

hybridizations and other hybridizations 

occur is not well known’’ (Ref. 42). 

Regarding the weedy tendencies of this 

genus, one expert indicated that ‘‘nine 

species are reported as naturalized or 

persistent in California... but most 

occupy disturbed sites near cultivated 

or urbanized areas’’ (Ref. 42). Another 

expert said, ‘‘It seems possible that in 

Mediterranean climates Pelargonium 

could become a weed problem’’ (Ref. 

42). Two other experts thought that 

acquisition of virus resistance would 

not affect the weedy tendencies of this 

genus. One said, ‘‘Pelargonium species 

are notoriously poor seed producers and 

are all also native to Africa, particularly 

South Africa. They have specialized 

ecological niches that would not easily 

be available anywhere in the U.S. or its 

territories. California is the most likely 

place where this could happen, and no 

incidence of an adventive Pelargonium 

has ever been reported. Viral resistance 

would not mitigate these factors that 

prevent adventive establishment’’ (Ref. 

42). 

EPA is inclined to include hyacinth 

(Hyacinthus spp.) on the list in 

§ 174.27(a)(1) on the basis of 

information received from consultations 

with hyacinth experts. However, EPA is 

seeking any information from the public 

that would enable the Agency to 

complete its assessment of the potential 

for hyacinth to naturalize. Three experts 

consulted indicated that this genus does 

not form viable hybrids in nature with 


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wild or weedy relatives in the United 

States. Two experts indicated that there 

are no naturalized species of Hyacinthus 

in the United States, although a third 

said, ‘‘Hyacinthus orientalis has been 

reported as naturalized in the Blackland 

Prairies of Texas,’’ but details were not 

available (Ref. 42). All three experts 

agreed that acquired virus resistance is 

unlikely to make hyacinth become feral 

or spread into non-crop areas. 

On the basis of expert consultation, 

EPA has concluded that guava (Psidium 

guajava) does not meet the low risk 

standard needed for inclusion on the 

§ 174.27(a)(1) list. Two experts 

indicated that more research is needed 

to establish the potential for outcrossing 

with wild or weedy relatives. All three 

experts reported that guava is known to 

become feral or easily spread into noncrop areas in the United States. One 

expert stated, ‘‘Guava is a vigorous, 

common, weed in both warm to cool 

climates. It would likely give this plant 

additional competitive advantage with 

transgenic resistance to viruses’’ (Ref. 

42). However, another expert believed 

that ‘‘[g]uava is easily spread without 

having transgenic resistance. It does not 

appear that containing resistance to one 

or more virus [sic] would enhance its 

ability to become feral’’ (Ref. 42). EPA 

requests commenters who believe guava 

would be appropriate to include on the 

list in § 174.27(a)(1) specifically to 

address whether there are wild or 

weedy relatives with which guava could 

form viable hybrids in nature in the 

United States (including Puerto Rico, 

the Virgin Islands, Guam, the Trust 

Territory of the Pacific Islands, and 

American Samoa) and to address the 

concern that guava is a weedy species 

and acquisition of virus resistance could 

exacerbate these tendencies. Please 

provide literature citations or other 

evidence to support any claims contrary 

to EPA’s expert consultations. 

EPA believes that more information 

about lily (Lilium spp.) is needed to 

address issues raised by expert 

consultation conducted after 

recommendation from other flower 

experts. EPA is seeking any information 

from the public that would enable the 

Agency to complete its assessment of 

the potential for lily to become feral or 

spread into non-crop areas and the 

impact that acquired virus resistance 

might have on this potential. The 

experts agreed that in the United States 

the likelihood of a species in the genus 

Lilium forming viable hybrids in nature 

with a wild or weedy relative was very 

small given that lilies do not cross 

readily. ‘‘This is especially true for the 

hybrids that are adapted or selected for 

the intensive greenhouse or irrigated 

gardens’ environment. These lilies do 

not form successful colonies outside 

these specific environments. The chance 

that genes will be transferred from 

gardens to wild populations is 

negligible’’ (Ref. 42). However, 

regarding the weedy tendencies of this 

genus, one expert said ‘‘Several species 

of Asian or European origin are 

sporadically naturalized following 

escape from cultivation, but none strays 

far or is widespread or common enough 

to be considered a pest.... Lilium 

longiflorum (Easter lily; Japan) has been 

recorded from Utah and Florida’’ (Ref. 

42). Another expert said, ‘‘Lilium 

[formosanum] (Taiwan lily) has been 

known to invade natural habitats in 

Northern and Eastern Australia.... 

Caution would be advised in 

introducing L. [formosanum] into... the 

US’’ (Ref. 42). Two experts believed it 

unlikely that acquired virus resistance 

would affect the likelihood of lilies 

becoming feral, although a third said, 

‘‘Virus resistance might increase the 

speed and degree with which these 

exotic species might naturalize’’ (Ref. 

42). 

EPA is inclined to include nectarine 

and peach (Prunus persica) on the list 

in § 174.27(a)(1) on the basis of 

information received from expert 

consultations. However, EPA is seeking 

any information from the public that 

would enable the Agency to complete 

its assessment of the potential for a 

PVCP-PIP to introgress into a population 

of a wild or weedy relative or a 

naturalized population of the species 

and what effect such introgression 

might have. Specifically, the experts 

indicated that natural hybrids may be 

able to form with some other stone fruit 

trees (Ref. 42). However, if such trees 

are likely to be found in commercial 

cultivation, natural hybrids would not 

necessarily be expected in areas outside 

of managed orchards. Regarding 

whether Prunus persica is a weedy 

species, three of the four experts 

mentioned that nectarines and peaches 

are able to form feral populations (Ref. 

42). Nevertheless, three of the four 

experts indicated that they believed it 

would be unlikely that Prunus persica’s 

weedy tendencies, if any, would be 

exacerbated if it acquired transgenic 

resistance to one or more viruses. One 

expert said, ‘‘Generally the viruses are 

not the limiting factor to the 

establishment of feral peaches. The 

limiting factors are fungal and bacterial 

diseases that kill the plants before they 

can reproduce’’ (Ref. 42). The fourth 

expert said, ‘‘I would expect that the 

acquisition of virus resistance would 

enhance the spread of feral populations 

but would suggest that other causes of 

death, such as peach tree short life, 

bacterial canker and Armillaria Root 

Rot, are likely to be a more significant 

limitation to the spread and longevity of 

a feral nectarine tree’’ (Ref. 42). 

EPA believes that more information 

about olive (Olea europaea) is needed to 

address issues raised during expert 

consultation. Two experts indicated that 

hybridization with a wild or weedy 

relative has not been documented in the 

United States (Ref. 42). Both of these 

experts indicated that olive can 

naturalize. However, they disagreed 

about the frequency with which this is 

likely to occur. One expert suggested 

olive frequently forms reproducing and 

sustaining populations in non-crop 

areas and that it was ‘‘highly likely’’ that 

olive would become feral or easily 

spread into non-crop areas if it acquired 

transgenic resistance to one or more 

viruses because ‘‘O. europaea seeds are 

very viable and dispersed by rodents’’

(Ref. 42). However, another said, ‘‘It is 

highly unlikely that olives would 

become strongly feral or widely spread 

because the seeds are infrequently 

spread far from the tree, have a low 

reproduction rate due to poor seed 

germination and have a high rate of feral 

seedling mortality. Further, as a slow 

growing tree olives do not spread 

rapidly’’ (Ref. 42). The 2005 SAP also 

commented on including olives in the 

list of plants in § 174.27(a)(1). They 

noted olives have reportedly formed 

‘‘feral olive infestations in the Channel 

Islands National Park, and in oak 

woodlands and forest on Sonoma Valley 

and Davis, CA. In California, olive is 

‘considered an invasive exotic’ that 

‘compete[s] with native flora’ (personal 

communication)’’ (Ref. 42). EPA 

believes that before olive could be 

added to the list of plants in 

§ 174.27(a)(1), the Agency would need 

information to resolve the question of 

how weedy olive is in the United States 

and the effect virus resistance would 

have on any feral populations of olive 

that could acquire a PVCP-PIP from 

cultivated olive. 

EPA has received one response from 

a parsley expert suggesting that parsley 

(Petroselinum crispum) meets the 

requirements for inclusion on the list in 

§ 174.27(a)(1). This consultation 

indicates that parsley meets the three 

conditions outlined above by the SAP: 

it does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make parsley weedy or 

invasive. The breeder noted that parsley 


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could form viable hybrids with feral 

populations of parsley, but ‘‘parsley 

populations are generally quite shortlived away from cultivation and 

typically are not self-sustaining’’ (Ref. 

42). He also noted, ‘‘I would not expect 

parsley to become more easily spread 

with the acquisition of virus resistance. 

Although I’m aware that parsley is a 

host to celery mosaic virus and carrot 

motley dwarf, I have not known these 

viruses to be common limiting factors in 

parsley growth or reproduction, at least 

not here at our genebank in Iowa. 

Fungal diseases and insects are much 

more important’’ (Ref. 42). EPA is 

seeking public comment on this 

determination because the Agency 

desires a more robust response base. 

EPA is inclined to include petunia 

(Petunia spp.) on the list in 

§ 174.27(a)(1) on the basis of 

information received from consultations 

with petunia experts. However, EPA is 

seeking any information from the public 

that would enable the Agency to 

complete its assessment of the weedy 

characteristics of petunia and the 

likelihood that acquired virus resistance 

could cause petunia to become feral or 

easily spread into non-crop areas. The 

experts indicated that this genus does 

not form viable hybrids in nature with 

wild or weedy relatives in the United 

States. However, two of the three 

experts indicated that petunia has 

formed reproducing and sustaining 

populations in non-crop areas while 

noting that such populations have not 

required weed management activity. All 

three experts indicated that acquired 

virus resistance is unlikely to change 

the status quo. However, one noted that, 

‘‘as viruses affect petunia vigor, 

resistance might conceivably increase 

the odds’’ (Ref. 42). 

EPA is inclined to include pistachio 

(Pistacia vera) on the list in 174.27(a)(1) 

on the basis of information received 

from two expert consultations. 

However, EPA is seeking any 

information from the public that would 

enable the Agency to complete its 

assessment of the potential for a PVCPPIP to introgress into a population of a 

wild or weedy relative or a naturalized 

population of the species and what the 

impact of acquired virus resistance is 

likely to be. Specifically, the experts 

indicated several crosses have been 

reported in the literature, suggesting 

‘‘that potentially P. vera genes can 

eventually be transmitted to other 

species in the form of gene flow.’’

However, hybrids are only rarely formed 

as ‘‘they are isolated phenologically....’’

Nevertheless, one expert also indicated, 

‘‘There are a lot of unknowns in the 

phenology and cross-compatibility of 

different species of pistachio’’ (Ref. 42). 

Both experts indicated that ferality in 

pistachio is rare. One suggested it was 

not possible to say what the likelihood 

would be that pistachio would become 

feral or easily spread into non-crop 

areas if it acquired transgenic virus 

resistance. However the other said, ‘‘It is 

very unlikely pistachio would be widely 

feral as the primary method of spread, 

drop from the tree, results in a large 

percentage (>95%) of the nuts 

degrading, so they do not sprout. 

Further, the nuts do not go a long 

distance when they drop, localizing 

spread if sprouting does occur. Finally, 

if birds do remove a nut with a viable 

embryo from the tree they generally 

destroy it by eating...’’ (Ref. 42). 

EPA is inclined to include plum 

(Prunus domestica) on the list in 

§ 174.27(a)(1) on the basis of 

information received from expert 

consultations. However, EPA is seeking 

any information from the public that 

would enable the Agency to complete 

its assessment of the potential for a 

PVCP-PIP to introgress into a population 

of a wild or weedy relative or a 

naturalized population of the species. 

Specifically, the experts indicated that 

several native plum species occur in the 

United States. However, one indicated 

that because ‘‘P. domestica is a 

hexaploid, it would not cross with 

native Prunus plum species, which are 

all diploid’’ (Ref. 42). In addition, if any 

hybrids between cultivated plum and 

wild American plum species did occur, 

they ‘‘would not be fertile because of the 

chromosome number difference.’’ EPA 

thus believes that the risk of 

introgressing a PVCP-PIP into a wild or 

weedy population through gene transfer 

in the United States is very low. 

Regarding whether plum is a weedy 

species, one expert mentioned that 

although he had not personally 

observed it, he ‘‘heard from others that 

domestica... [is] found naturalized 

particularly in New England and 

Oregon. Some of these species tend to 

be easily spread by root suckers, and are 

better able to compete as weeds. Likely 

they only survive on roadsides and 

unmanaged areas, and could be easily 

killed if desired’’ (Ref. 42). Nevertheless, 

all three of the experts indicated that 

they believed it would be unlikely that 

plum’s weedy tendencies, if any, would 

be exacerbated if it acquired transgenic 

resistance to one or more viruses. 

According to one expert, ‘‘I doubt 

viruses are the only thing which 

restricts domestica from spreading more 

than it already has’’ (Ref. 42). According 

to another, ‘‘Currently virus diseases are 

not the most important limiting diseases 

for plum in the U.S. Other fungal and 

bacterial diseases are the limiting factors 

and cause death of uncared for 

commercial plums. Therefore transgenic 

plums with virus resistance would still 

be very susceptible to these limiting 

fungal and bacterial diseases’’ (Ref. 42). 

EPA has received one response from 

a spinach expert suggesting that spinach 

(Spinacia oleracea) meets the 

requirements for inclusion on the list in 

§ 174.27(a)(1). This consultation 

indicated that spinach meets the three 

conditions outlined above by the SAP: 

it does not have wild or weedy relatives 

in the United States with which it can 

form viable hybrids in nature, it is not 

currently weedy or invasive in the 

United States, and there is no reason to 

believe that acquisition of virus 

resistance would make spinach weedy 

or invasive. The expert noted, 

‘‘Transgenic viral resistance alone 

probably would not make spinach 

survive wild conditions, because there 

are other fungus (e.g. downy mildew, 

Stemphylium leaf spot) diseases and 

bacterial diseases (e.g. bacterial leaf 

spot), as well as drought resistance and 

competing ability issues’’ (Ref. 42). EPA 

is seeking public comment on this 

determination because the Agency 

desires a more robust response base. 

EPA believes that more information 

about taro (Colocasia esculenta) is 

needed to address issues raised by 

expert consultation. For example, 

although experts knew of no weedy 

relatives with which taro might cross, 

‘‘crossing is theoretically possible 

among all of the taros’’ (Ref. 42). One 

expert indicated that ‘‘taro can flower 

naturally in places such as Kula in 

Maui, Hawaii. The climate there allows 

taro to flower naturally, whereas in 

other places it is often necessary to 

induce flowering with hormone 

applications. Furthermore, hybrids 

made by cross-fertilization are viable. It 

is entirely possible for taro to survive in 

the wild in tropical and subtropical 

climates. Most taros would succumb 

because taro has been cultivated for so 

long that it is mostly dependent on 

humans to compete with many weeds. 

By itself it is almost always outcompeted by weeds and dies out. But 

theoretically it can survive, it can crosspollinate and form viable progeny’’ (Ref. 

42). Regarding whether taro is known to 

become feral or easily spread in noncrop areas, one expert said, ‘‘YES, but 

only in favorable conditions of adequate 

warmth and moisture.’’ Another expert 

indicated that ‘‘taro is considered an 

invasive species in certain places 

(Florida)’’ (Ref. 42). Regarding whether 

acquired transgenic resistance to one or 

more viruses could change taro in this 


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respect, the experts disagreed. One 

expert said, ‘‘It is highly unlikely that 

taro with acquired transgenic resistance 

would spread to non-crop areas because 

the probability of crossing is extremely 

small. Through vegetative propagation it 

will require man intervention just as 

non-transgenic plants.’’ Another expert 

said, ‘‘Taro has many pests, including 

viruses, that restricts [sic] its ability to 

compete with more weedy plant 

species. Resistance to any of these pests 

would increase its competitiveness but 

this is not likely to turn taro into a weed 

problem.’’ However, the third expert 

said, ‘‘With resistance to one or more 

virus diseases, taro would become 

hardier. That is the reason for breeders 

to go to the trouble of developing 

disease-resistant plants. A hardier taro 

is more likely to be successful and 

survive as an escaped cultivated 

species. It has already been seen that 

taro has become feral in certain parts of 

Florida. With added resistance, it would 

be more likely to survive in the wild, 

provided that resistance gives it some 

advantage. In other words, if the virus 

disease is important, resistance is 

valuable. In Thailand, the taro plants 

that one can find along roadsides (feral) 

possess a high degree of resistance to 

taro leaf blight, the most destructive 

disease of cultivated taro there. Those 

that don’t possess resistance don’t stand 

much of a chance to survive on their 

own’’ (Ref. 42). EPA believes that before 

taro could be added to the list of plants 

in § 174.27(a)(1), the Agency would 

need information to evaluate the 

likelihood that feral populations of taro 

could acquire a PVCP-PIP from 

cultivated taro and to evaluate whether 

acquisition of virus resistance is likely 

to increase taro’s likelihood of forming 

feral populations. 

EPA believes that more information 

about tomato (Solanum lycopersicum) is 

needed to address issues raised by 

several experts that EPA consulted. For 

example, three of four experts indicated 

that tomato is able to form viable 

hybrids in nature in the United States 

with its putative progenitor Solanum 

lycopersicum var. cerasiforme. These 

experts indicated the hybrids formed are 

fertile, self-compatible, and freely 

intercross due to highly compatible 

phenology. However, a third expert 

indicated that ‘‘[a]lthough crosses can 

occur between wild species and 

cultivated tomato, usually with human 

intervention, the direction of the cross 

is such that the wild species has to be 

the male parent.... If the cultivated 

tomato has the transgene, transfer to 

wild species via pollen will not 

happen’’ (Ref. 42). EPA is not however 

interested solely in whether transfer 

occurs via pollen, but whether a 

transgene could introgress into a wild 

population through a hybrid 

intermediate. Three of four experts also 

indicated that tomato is able to form 

feral populations in the United States 

(including Puerto Rico, the Virgin 

Islands, Guam, the Trust Territory of the 

Pacific Islands, and American Samoa), 

although one expert pointed out that 

neither virus-resistant cultivars nor 

resistant wild relatives have 

demonstrated a greater propensity to 

become feral, suggesting that acquisition 

of a PVCP-PIP may not exacerbate 

whatever weedy tendencies exist in 

tomato. However, another expert 

suggested that this question would have 

to be tested in the field under controlled 

conditions. EPA believes that before 

tomato could be added to the list of 

plants in § 174.27(a)(1), the Agency 

would need information to evaluate the 

effect of virus resistance on any wild or 

weedy populations of tomato that could 

acquire a PVCP-PIP from cultivated 

tomato and to evaluate whether 

acquisition of virus resistance is likely 

to exacerbate tomato’s weedy 

tendencies. 

EPA believes that more information 

about watermelon (Citrullus lanatus) is 

needed to address issues raised by 

expert consultation. For example, 

experts indicated that watermelon is 

able to cross with C. lanatus var. 

citroides. Moreover, one expert 

indicated hybrids made by crossfertilization are sexually fertile and 

demonstrate ‘‘[m]ore vigor compared 

with cultivated watermelon (C. lanatus 

var. lanatus)’’ (Ref. 42). Regarding 

whether watermelon is known to 

become feral or easily spread in noncrop areas, one expert indicated that 

escaped plants are able to form 

reproducing and sustaining populations 

in non-crop areas, although this occurs 

rarely and has not required weed 

management activity outside of crop 

areas (Ref. 42). Regarding whether 

acquired transgenic resistance to one or 

more viruses could change watermelon 

in this respect, one expert indicated this 

was ‘‘[u]nlikely. Watermelons have few 

viruses that kill the plant or decrease its 

reproductive activity. Therefore, gaining 

virus resistance will not likely increase 

it’s [sic] reproductive success in feral 

populations’’ (Ref. 42). Another expert 

said, ‘‘Virus pressure would likely be far 

less in feral populations than in 

cultivated fields due to differences in 

time of germination, rate of growth, 

population density, [and] reduced 

numbers of aphid vectors’’ (Ref. 42). 

EPA believes that before watermelon 

could be added to the list of plants in 

§ 174.27(a)(1), the Agency would need 

information to evaluate the likelihood 

that wild populations of C. lanatus var. 

citroides or feral populations of C. 

lanatus var. lanatus could acquire a 

PVCP-PIP from cultivated watermelon 

and what effect this acquisition might 

have. 

EPA believes that more information 

about wishbone flower (Torenia spp.) is 

needed to address issues raised by 

expert consultation. EPA is seeking any 

information from the public that would 

enable the Agency to complete its 

assessment of the potential for a PVCPPIP to enhance the potential of species 

in this genus to naturalize. All three 

experts consulted indicated that Torenia 

species do not form viable hybrids in 

nature with wild or weedy relatives in 

the United States. However, all 

indicated that Torenia has naturalized 

in certain areas of the United States. 

One expert said, ‘‘Torenia fournieri has 

been reported to naturalize by seed in 

Florida and Louisiana, but it is not clear 

to what extent. I personally have 

observed re-seeding in garden settings. 

Given the rising popularity of Torenia in 

American horticulture, there is probable 

cause for concern in the deep south, 

California and Hawaii. However, the 

species in cultivation are heat sensitive 

and moisture-demanding, which would 

probably limit the extent to which they 

can naturalize’’ (Ref. 42). Expert 

consultations also suggest that not 

enough information is known about the 

potential of virus resistance to affect the 

plant’s weedy tendencies. One expert 

said, ‘‘I do not know to what extent 

viruses impact Torenia fournieri. It is 

conceivable that viral resistance could 

increase fecundity’’ (Ref. 42). 

EPA is not proposing to include 

celery (Apium graveolens), kiwi 

(Actinidia spp.), or okra (Abelmoschus 

esculentus) on the list in § 174.27(a) 

because the Agency was unable to 

complete any expert consultations on 

these crops. EPA is therefore seeking 

information from the public to address 

whether such crops could qualify for 

inclusion on the list. 

EPA also requests comment on the 

weediness potential of squash 

(Cucurbita pepo) and any wild or weedy 

relatives in the United States that could 

acquire a PVCP-PIP from cultivated 

squash through gene flow. 

2. EPA requests comment on the 

Agency’s options for the weediness 

criterion in § 174.27(a)(2) discussed in 

Unit III.C.2.iii. Specifically, the Agency 

is considering whether it is more 

appropriate to evaluate the potential for 

a crop to form ‘‘viable hybrids’’ or 


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‘‘viable, fertile hybrids’’ in nature with 

a wild or weedy relative. 

In addition, EPA is considering 

whether it is necessary to evaluate 

whether the plant containing the PIP is 

unlikely to establish weedy or invasive 

populations outside of agricultural 

fields in the United States even if the 

plant contains a PVCP-PIP, assuming 

that the plant has no wild or weedy 

relatives in the United States with 

which it can form viable hybrids in 

nature and it is not a weedy or invasive 

species outside of agricultural fields in 

the United States. 

EPA also requests comment on 

language for the criterion in 

§ 174.27(a)(2) (e.g., such as under option 

four) that would allow EPA to broadly 

consider the effect that virus resistance 

might have on wild or weedy plant 

populations that could acquire the 

PVCP-PIP. Under such an approach, the 

individual determinations that the 

Agency would make would likely 

require data to be generated that would 

not normally occur as a routine part of 

product development (but may be 

developed for a review by USDA/ 

APHIS). Such determinations are likely 

to involve similar amounts of effort as 

registration reviews, but they would 

provide a means whereby a PVCP-PIP 

could be exempted even if used in a 

plant that has wild or weedy relatives in 

the United States. The Agency requests 

commenters to indicate how 

controversial individual determinations 

using such language as under option 4 

are likely to be, as the Agency would 

like to have an exemption procedure 

that requires only one public notice (see 

Unit III.A.2.). 

3. EPA requests comment on the 

merits of incorporating the use of 

biocontainment and/or bioconfinement 

techniques into § 174.27(a), such that 

PVCP-PIPs deployed in tandem with 

such technology could be determined to 

meet the weediness criterion. Please see 

the discussion of this option in Unit 

III.C.3., which articulates several issues 

associated with such an option and 

suggests regulatory language that might 

be used. 

4. EPA requests comment on the 

Agency’s use of the term ‘‘weedy.’’ EPA 

uses the term in two different contexts: 

in ‘‘wild or weedy relatives’’ and in 

‘‘weedy or invasive species.’’ However, 

the Agency notes that the term has a 

different meaning in each context. 

When discussing a ‘‘wild or weedy 

relative,’’ EPA considers weedy plants 

to be those with the characteristics of 

weeds, i.e., those that are considered 

undesirable, unattractive, or 

troublesome, especially when growing 

where they are not wanted. However, 

when discussing ‘‘weedy or invasive 

species,’’ EPA considers a weedy 

species to be a species that is an 

aggressive competitor in natural 

ecosystems. EPA recognizes that it 

would be better to have a single 

definition of the term ‘‘weedy,’’ but the 

Agency believes both meanings of the 

term ‘‘weedy’’ are in common, scientific 

usage. In addition, the Agency is not 

aware of a term other than ‘‘wild or 

weedy relative’’ that would encompass 

all plants that grow outside of 

agricultural fields, or a term other than 

‘‘weedy or invasive species’’ that would 

encompass all of the plants that are 

problematic from a management 

perspective. EPA would be particularly 

interested in alternative suggestions to 

describe each of these situations and 

thus enable the Agency to avoid using 

two different meanings for the word 

‘‘weedy.’’

5. EPA requests comment on whether 

the viral interactions criterion in 

§ 174.27(b)(1)(i) could be expanded to 

read ‘‘the viral pathotype used to create 

the PVCP-PIP has naturally infected 

plants in the United States or other 

parts of North America and naturally 

infects plants of the same species as 

those containing the PVCP-PIP.’’ EPA 

recognizes that viruses are likely to 

move freely across political boundaries. 

Thus, limiting this criterion to viruses 

that have naturally infected plants ‘‘in 

the United States or other parts of North 

America’’ may be most appropriate 

limitation for avoiding the introduction 

of sequences from an exotic virus into 

the United States through creation of a 

PVCP-PIP. 

6. EPA requests comment on whether 

it is necessary for the Agency to address 

viral interactions, i.e., recombination, as 

articulated in § 174.27(b), in order for 

the Agency to conclude that a PVCP-PIP 

is low risk. EPA requests commenters to 

indicate whether their comments apply 

to RNA viruses, DNA viruses, or both. 

The Agency notes that a large number 

of PVCP-PIPs are likely to meet 

§ 174.27(b) as proposed. EPA therefore 

requests commenters who believe 

§ 174.27(b) is unnecessary to focus their 

remarks on why those PVCP-PIPs that 

do not meet the conditions of proposed 

§ 174.27(b) would pose low risk with 

respect to recombination rather than 

addressing the average risk associated 

with PVCP-PIPs as a whole. 

For the PVCP-PIPs that would only 

qualify for an exemption without the 

limitations provided by § 174.27(b), EPA 

does not believe the Agency can 

conclude low risk with respect to 

recombination (as the Agency must do 

in order to remove § 174.27(b) entirely) 

because the 2004 and 2005 SAPs have 

identified specific instances where this 

general conclusion may not hold. 

Nevertheless, EPA is considering 

removing this criterion in whole or in 

part if the Agency receives information 

suggesting that such factors as 

articulated and as incorporated into 

§ 174.27(b) are unnecessary for 

concluding a particular PVCP-PIP is low 

risk. For example, the Agency notes that 

the current global movement of goods 

and people likely results in the at least 

occasional transport of plant viruses 

great distances from their original 

geographic distribution in spite of 

governmental efforts to limit their 

movement. In such a context, the 

Agency questions the relevance of 

requiring as a condition of exemption 

that the viral pathotype used to create 

the PVCP-PIP has naturally infected 

plants in the United States. 

7. EPA requests comment on whether 

the protein production criterion in 

§ 174.27(c)(1)(i) could be modified to 

encompass other types of PVCP-PIP 

constructs that mediate resistance based 

on PTGS. According to today’s proposal, 

any such constructs other than those 

inserted only in an inverted repeat 

orientation or lacking a start codon 

would be reviewed by the Agency for 

lack of protein production under 

§ 174.27(c)(2). However, if the Agency 

could identify additional types of 

constructs that would present 

reasonable assurance that no protein 

would be produced in any plant tissues 

at any point in the plant’s 

developmental cycle, including if PTGS 

were to be suppressed, such constructs 

could be included under 

§ 174.27(c)(1)(i) and would not require 

Agency review to verify that no protein 

would be produced. 

8. EPA requests comment on whether 

the Agency could extend the proposed 

exemption (including regulatory text 

and rationale as written) to other PIPs 

that are based on any plant virus gene 

that confers virus resistance when no 

protein is produced from the inserted 

virus sequence because it is inserted 

only in an inverted repeat orientation 

and/or it lacks an initiation codon for 

protein synthesis. The 2005 SAP noted 

that ‘‘[o]ther PIPs conferring virus 

resistance should be evaluated similarly 

as are the PVCP-PIPs, if the PIPs mode 

of action is via PTGS’’ (Ref. 11). 

However, the Panel also mentioned 

several risk concerns associated with 

specific virus proteins. The Agency 

therefore concluded that PTGS was a 

necessary but not sufficient condition 

for expanding the exemption to other 

types of virus gene-based PIPs given that 

protein can be produced under certain 

circumstances from many constructs 


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that employ PTGS, and the Agency does 

not currently have sufficient 

information to conclude that such 

protein would pose low risk to the 

environment. In the case of the two 

types of inserts described above, the 

2005 SAP indicated that it could be 

‘‘safely determined’’ that no protein 

would ever be produced from such 

constructs (Ref. 11), and they would 

meet § 174.27(b) and (c). Section 

174.27(a) would be evaluated as it is 

evaluated for PVCP-PIPs given that the 

relevant consideration would be the 

virus-resistant phenotype of the plant 

rather than the means by which the trait 

is conferred. EPA thus believes that the 

criteria in today’s proposed exemption 

address all relevant risk considerations 

for PIPs based on any plant virus gene 

when no protein is produced from the 

inserted virus sequence. EPA is 

therefore inclined to expand the 

exemption to include PIPs based on any 

viral gene that confers virus resistance 

if the PIP meets § 174.27(a) and no 

protein is produced from the inserted 

virus sequence because it is inserted 

only in an inverted repeat orientation 

and/or it lacks an initiation codon for 

protein synthesis. 

9. EPA requests comment on the 

alternative approach the Agency is 

considering for exempting marker genes 

that are used as inert ingredients with 

PIPs under which NPTII, GUS, and PMI 

would be exempt from FIFRA when 

used as inert ingredients with any 

exempt PIP, regardless of the plant in 

which they are expressed (as discussed 

in Unit IV). 

10. EPA requests comment on the 

possibility of developing an Agencydetermined approach for exempting 

inert ingredients under FIFRA. Under 

this approach, EPA would propose new 

language at 40 CFR 174.21(c) that would 

enable the Agency to review inert 

ingredients on a case-by-case basis to 

determine whether they meet the 

standard established for inert 

ingredients in 40 CFR part 174 subpart 

X-List of Approved Inert Ingredients. 

EPA is considering such a procedure to 

ensure that a low-risk PVCP-PIP that 

otherwise meets the conditions for 

exemption at § 174.21 would not require 

a FIFRA registration solely due to the 

presence of an inert ingredient that may 

prove to be low risk upon review. The 

only alternative to registration for such 

a PVCP-PIP would be to add the inert 

ingredient to the list through 

rulemaking under FIFRA section 25(b), 

such that the PVCP-PIP could be 

exempted. Rulemaking would take 

considerably longer than an Agency 

determination procedure like that 

described in today’s proposal for other 

exemption criteria. 

The criteria that EPA is considering 

for determining whether an inert 

ingredient would be exempt under an 

Agency determination are: 

i. The inert ingredient is non-toxic to 

humans and animals and does not 

produce a toxic substance, 

ii. The inert ingredient is nonallergenic, and 

iii. If the inert ingredient is an 

antibiotic resistance gene or marker 

protein, therapy with antibiotics would 

not be compromised even if the gene 

were to be transferred from plants to 

microorganisms in the gut of man or 

animal, or in the environment. 

11. EPA requests comment on the 

Agency’s assumption in the economic 

analysis for this proposed rule that the 

estimated number of PVCP-PIPs 

submitted for regulatory review will be 

the same per year over the next 10 years. 

EPA assumed a uniform distribution 

given that the Agency lacks reliable 

information on which to base a more 

complex distribution pattern. EPA is 

particularly interested in any data or 

information supporting a different 

assumption for the economic analysis. 

12. EPA requests comment on the 

usefulness of a guidance document that 

would provide a simplified description 

of the final rule. EPA intends to develop 

such a document and is interested to 

know what specific content the public 

would find most helpful. 

VIII. References 

The following books, articles, and 

reports were used in preparing this 

proposed rule and are cited in this 

document by the number indicated. 

1. Callaway, A., Giesman–Cookmeyer, 

D., Gillock, E.T., Sit, T.L., Lommel, S.A. 

The multifunctional capsid proteins of 

plant RNA viruses. Annual Review of 

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2. Kaniewski, W.K., Lawson, C. Coat 

protein and replicase–mediated 

resistance to plant viruses. In: Hadidi, 

A., Khetarpal, R.K., Koganezawa, H. 

Plant Virus Disease Control. St. Paul, 

Minnesota: APS Press, 1998:65–78. 

3. Powell, P.A., Sanders, P.R., Tumer, 

N., Fraley, R.T., Beachy, R.N. Protection 

against tobacco mosaic virus infection 

in transgenic plants requires 

accumulation of coat protein rather than 

coat protein RNA sequences. Virology 

1990; 175:124–30. 

4. Goldbach, R., Bucher, E., Prins, M. 

Resistance mechanisms to plant viruses: 

an overview. Virus Research 2003; 

92:207–12. 

5. Savenkov, E.I., Valkonen, J.P.T. 

Silencing of a viral RNA silencing 

suppressor in transgenic plants. Journal 

of General Virology 2002; 83:2325–35. 

6. Waterhouse, P.M., Wang, M.B., 

Lough, T. Gene silencing as an adaptive 

defence against viruses. Nature 2001; 

411:834–42. 

7. Kooter, J.M., Matzke, M.A., Meyer, 

P. Listening to the silent genes: 

transgene silencing, gene regulation and 

pathogen control. Trends in Plant 

Science 1999; 4:340–7. 

8. Hamilton, A.J., Baulcombe, D.C. A 

species of small antisense RNA in 

posttranscriptional gene silencing in 

plants. Science 1999; 286:950–2. 

9. Lu, R., Martin–Hernandez, A.M., 

Peart, J.R., Malcuit, I., Baulcombe, D. 

Virus–induced gene silencing in plants. 

Methods 2003; 30:296–303. 

10. National Research Council. 

Genetically Modified Pest–Protected 

Plants: Science and Regulation. 

Washington, DC: National Academy 

Press, 2000. 

11. FIFRA Scientific Advisory Panel. 

Minutes of the December 6–8, 2005 

Meeting on Plant–Incorporated 

Protectants Based on Virus Coat Protein 

Genes: Science Issues Associated with 

the Proposed Rule. 2005. 

12. Bartsch, D., Schmidt, M., Pohl–

Orf, M., Haag, C., Schuphan, I. 

Competitiveness of transgenic sugar beet 

resistant to beet necrotic yellow vein 

virus and potential impact on wild beet 

populations. Molecular Ecology 1996; 

5:199. 

13. National Research Council. Field 

Testing Genetically Modified 

Organisms. Washington, DC: National 

Academy Press, 1989. 

14. Keeler, K.H. Can genetically 

engineered crops become weeds? Bio/ 

Technology 1989; 7:1134–9. 

15. National Research Council. 

Environmental Effects of Transgenic 

Plants: The Scope and Adequacy of 

Regulation. Washington, DC: National 

Academy Press, 2002. 

16. Wennstrom, A. Risk assessment of 

genetically modified undomesticated 

plants. In: den Nijs, H.C.M., Bartsch, D., 

Sweet, J. Introgression from Genetically 

Modified Plants. Cambridge, MA: CABI 

Publishing, 2004:297–307. 

17. Levin, D.A. The origin of isolating 

mechanisms in flowering plants. 

Evolutionary Biology 1978; 11:185–317. 

18. Ellstrand, N.C., Prentice, H.C., 

Hancock, J.F. Gene flow and 

introgression from domesticated plants 

into their wild relatives. Annual Review 

of Ecology and Systematics 1999; 

30:539–63. 

19. Ellstrand, N. Dangerous Liaisons. 

Baltimore: Johns Hopkins University 

Press, 2003. 

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Paris: OECD, 1994:71–9. 

133. Berg, J., Tymoczko, J., Stryer, L., 

Clarke, N. Biochemistry, 5th ed. New 

York: W. H. Freeman and Company, 

2002. 

134. Stewart, C.N.Jr., Halfhill, M.D., 

Warwick, S.I. Transgene introgression 

from genetically modified crops to their 

wild relatives. Nature Reviews Genetics 

2003; 4:806–17. 

135. Bartsch, D., Brand, U., Morak, C., 

Pohl-Orf, M., Schuphan, I., Ellstrand, N. 

Biosafety of hybrids between transgenic 

virus-resistant sugar beet and swiss 

chard. Ecological Applications 2001; 

11:142–7. 

136. Spencer, L.J., Snow, A.A. 

Fecundity of transgenic wild-crop 

hybrids of Cucurbita pepo 

(Cucurbitaceae): implications for cropto-wild gene flow. Heredity 2001; 

86:694–702. 

137. Ilardi, V., Barba, M. Assessment 

of functional transgene flow in tomato 

fields. Molecular Breeding 2001; 8:311–

5. 

138. Fuchs, M., Chirco, E.M., 

Gonsalves, D. Movement of coat protein 

genes from a commercial virus-resistant 

transgenic squash into a wild relative. 

Environmental Biosafety Research 2004; 

3:5–16. 

139. Bartsch, D. Ecological impact of 

transgenic virus-resistance in crop, 

weed, and wild plant populations (due 

to potential alterations of plant 

invasiveness). In: Tepfer, M., Bala ́zs, E. 

Virus-resistant Transgenic Plants: 

Potential Ecological Impact. Berlin: 

Springer, 1997:107–13. 

140. Tepfer, M. Risk assessment of 

virus-resistant transgenic plants. Annual 

Review of Phytopathology 2002; 40:467–

91. 

IX. Content of Official Record 

EPA has established an official record 

for this rulemaking. The official record 

includes all information considered by 

EPA in developing this proposed rule 

including documents specifically 

referenced in this action, any public 

comments received during an applicable 

comment period, and any other 

information related to this action, 

including any information claimed as 

CBI and any information received in any 

of the related dockets mentioned below. 

This official record includes all 

information physically located in the 

dockets described in the following 

paragraph, as well as any documents 

that are referenced in the documents in 

the dockets. The public version of the 

official record does not include any 

information claimed as CBI. 

The complete official record for this 

rulemaking includes: 

The docket identified by the docket 

control number OPP–300370 for the 

document entitled ‘‘Proposed Policy: 

Plant-Pesticides Subject to the Federal 

Insecticide, Fungicide, and Rodenticide 

Act and the Federal Food, Drug, and 

Cosmetic Act’’ (59 FR 60496, November 

23, 1994)(FRL–4755–2). 

The docket identified by the docket 

control number OPP–300369 for the 

document entitled ‘‘Plant-Pesticides 

Subject to the Federal Insecticide, 

Fungicide and Rodenticide Act; 

Proposed Rule’’ (59 FR 60519, 

November 23, 1994)(FRL–4755–3). 

The docket identified by the docket 

control number OPP–300368 for the 

document entitled ‘‘Plant-Pesticides; 

Proposed Exemption From the 

Requirement of a Tolerance Under the 

Federal Food, Drug, and Cosmetic Act’’

(59 FR 60535, November 23, 1994)(FRL–

4758–8). 

The docket identified by the docket 

control number OPP–300371 for the 

document entitled ‘‘Plant-Pesticides; 

Proposed Exemption From the 

Requirement of a Tolerance Under the 

Federal Food, Drug, and Cosmetic Act 

for Nucleic Acids Produced in Plants’’

(59 FR 60542, November 23, 1994)(FRL–

4755–5). 

The docket identified by the docket 

control number OPP–300367 for the 

document entitled ‘‘Plant-Pesticides; 

Proposed Exemption From the 

Requirement of a Tolerance Under the 

Federal Food, Drug, and Cosmetic Act 

for Viral Coat Proteins Produced in 

Plants’’ (59 FR 60545, November 23, 

1994)(FRL–4755–4). 

The docket identified by the docket 

control number OPP–300370A for the 

document entitled ‘‘Plant-Pesticide 

Subject to the Federal Insecticide, 

Fungicide, and Rodenticide Act and the 

Federal Food, Drug, and Cosmetic Act; 

Reopening of Comment Period’’ (61 FR 

37891, July 22, 1996)(FRL–5387–4). 

The docket identified by the docket 

control number OPP–300368A for the 

document entitled ‘‘Plant-Pesticides; 

Supplemental Notice of Proposed 

Rulemaking’’ (62 FR 27132, May 16, 

1997)(FRL–5717–2). 

The docket identified by the docket 

control number OPP–300371A for the 

document entitled ‘‘Plant-Pesticides; 

Nucleic Acids; Supplemental Notice of 

Proposed Rulemaking’’ (62 FR 27142, 

May 16, 1997)(FRL–5716–7). 

The docket identified by the docket 

control number OPP–300367A for the 

document entitled ‘‘Plant-Pesticides; 

Viral Coat Proteins; Supplemental 

Notice of Proposed Rulemaking’’ (62 FR 

27149, May 16, 1997)(FRL–5716–6). 

The docket identified by the docket 

control number OPP–300369A for the 

document entitled ‘‘Plant-Pesticides, 

Supplemental Notice of Availability of 

Information’’ (64 FR 19958, April 23, 

1999)(FRL–6077–6). 

The docket identified by the docket 

control number OPP–300369B for the 

document entitled ‘‘Regulations Under 

the Federal Insecticide, Fungicide, and 

Rodenticide Act for Plant-Incorporated 

Protectants (Formerly Plant-Pesticides)’’

(66 FR 37772, July 19, 2001)(FRL–6057–

7). 

The docket identified by the docket 

control number OPP–300368 for the 

document entitled ‘‘Exemption From 


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the Requirement of a Tolerance Under 

the Federal Food, Drug, and Cosmetic 

Act for Residues Derived through 

Conventional Breeding From Sexually 

Compatible Plants of Plant-Incorporated 

Protectants (Formerly Plant-Pesticides)’’

(66 FR 37830, July 19, 2001)(FRL–6057–

6). 

The docket identified by the docket 

control number OPP–300371 for the 

document entitled ‘‘Exemption From 

the Requirement of a Tolerance Under 

the Federal Food, Drug, and Cosmetic 

Act for Residues of Nucleic Acids that 

are Part of Plant-Incorporated 

Protectants (Formerly Plant-Pesticides)’’

(66 FR 37817, July 19, 2001)(FRL–6057–

5). 

The docket identified by the docket 

control number OPP–300370B for the 

document entitled ‘‘Plant-Incorporated 

Protectants (Formerly Plant-Pesticides), 

Supplemental Proposal’’ (66 FR 37855, 

July 19, 2001)(FRL–6760–4). 

The docket identified by the docket 

control number EPA–HQ–OPP–2006–

0643 for the companion document 

entitled ‘‘Exemption from the 

Requirement of a Tolerance under the 

Federal Food, Drug, and Cosmetic Act 

for Residues of Plant Virus Coat Proteins 

that are Part of a Plant-Incorporated 

Protectant (PVC-Proteins)’’ (FRL–8100–

5) published elsewhere in this issue of 

the Federal Register. 

The docket identified by the docket 

control number EPA–HQ–OPP–2006–

0642 for this document (FRL–8100–7). 

Also included in the complete official 

record are: 

1. Public comments submitted in 

response to the proposals and 

supplemental documents cited in the 

above paragraph. 

2. Reports of all meetings of the 

Biotechnology Science Advisory 

Committee and the FIFRA Scientific 

Advisory Panel pertaining to the 

development of this proposed rule. 

3. The Economic Analysis for this 

proposed rule and supporting 

documents. 

4. Support documents and reports. 

5. Records of all communications 

between EPA personnel and persons 

outside EPA pertaining to the proposed 

rule. (This does not include any interand intra-agency memoranda, unless 

specifically noted in the indices of the 

dockets). 

6. Published literature that is cited in 

this document. 

X. Statutory and Executive Order 

Reviews 

A. Executive Order 12866 

Pursuant to Executive Order 12866, 

entitled Regulatory Planning and 

Review (58 FR 51735, October 4, 1993), 

the Office of Management and Budget 

(OMB) has determined that this is a 

‘‘significant regulatory action’’ because 

it may raise potentially novel legal or 

policy issues arising out of legal 

mandates, the President’s priorities, or 

the principles set forth in the Executive 

Order. Therefore, this action was 

submitted to OMBfor review, and 

changes made during that review have 

been documented in the docket. 

In addition, EPA has prepared an 

economic analysis of the impacts related 

to this proposed action. The economic 

analysis evaluates the 

quantifiablebenefits of exempting PVCPPIPs from FIFRA requirements (40 CFR 

part174) and discusses the nonquantifiable benefits of this action. 

Thiseconomic analysis is contained in a 

document entitled ‘‘EconomicAnalysis 

for Proposed Exemption Under the 

Federal Insecticide,Fungicide, and 

Rodenticide Act for Certain PlantIncorporatedProtectants Derived from a 

Plant Viral Coat Protein Gene (PVCPPIPs)’’(called here ‘‘the EA’’). This 

document is available in thedocket and 

is briefly summarized in Unit V. 

B. Paperwork Reduction Act 

Pursuant to the Paperwork Reduction 

Act (PRA), 44 U.S.C. 3501et seq., an 

Agency may not conduct or sponsor, 

and a person is notrequired to respond 

to a collection of information unless it 

displays acurrently valid OMB control 

number, or is otherwise required to 

submitthe specific information by a 

statute. The OMB control numbers for 

EPA’s regulations codified in Title 40 of 

the CFR, after appearing in the preamble 

of the final rule, are further displayed 

either by publication in the Federal 

Register or by other appropriate means, 

such as on the related collection 

instrument or form, if applicable. The 

display of OMB control numbers in 

certain EPA regulations is consolidated 

in a list at 40 CFR 9.1. 

The information collection 

requirements contained in thisproposed 

rule have been submitted to OMB for 

review and approvalunder the PRA in 

accordance with the procedures at 5 

CFR 1320.11.The burden and costs 

related to the information collection 

requirementscontained in this rule are 

described in an addendum to a 

currently approved Information 

Collection Request (ICR) identified as 

EPA ICR No. 1693.04 (OMB number 

2070–0142). As defined in the PRA, 

‘‘burden’’ means the total time, effort, or 

financial resources expended by persons 

to generate, maintain, retain, or disclose 

or provide information to or for a 

Federal agency. This includes the time 

needed to review instructions; develop, 

acquire, install, and utilize technology 

and systems for the purposes 

ofcollecting, validating, and verifying 

information, processing andmaintaining 

information, and disclosing and 

providing information;adjust the 

existing ways to comply with any 

previously applicableinstructions and 

requirements; train personnel to be able 

to respond toa collection of information; 

search data sources; complete and 

reviewthe collection of information; and 

transmit or otherwise disclose 

theinformation. 

This proposed rule includes 

information collection requirements 

ofdevelopers who wish to exempt 

PVCP-PIPs under the provisions of 

theproposed rule. Developers selfdetermining their exemption status 

willhave to develop and maintain 

records supporting their 

determinationand report their 

determination to EPA. Developers 

relying on Agencydetermination of 

exemption status will have to develop 

the informationneeded for the Agency 

determination and submit it to EPA. The 

Agencyhas estimated that this 

information collection has an estimated 

burdenof 21.5 hours per response for 

developer-determined exemptions 

and23.5 hours per response for Agencydetermined exemptions. EPAestimates 

that there will be one submission of 

each type per year fora total annual 

respondent burden of 45 hours. 

Direct your comments on the 

Agency’s need for this information, the 

accuracy of the provided burden 

estimates, and any suggested methods 

for minimizing respondent burden, 

including the use of automated 

collection techniques, to EPA using the 

public docket that has been established 

for this proposed rule (Docket ID No. 

EPA–HQ–OPP–2006–0642). In addition, 

send a copy of your comments about the 

ICR to OMB at: Office of Information 

and Regulatory Affairs, Office of 

Management and Budget, 725 17th St., 

NW., Washington, DC 20503, Attention: 

Desk Office for EPA ICR No. 2070–0142. 

Since OMB is required to complete its 

review of the ICR between 30 and 60 

days after April 18, 2007, please submit 

your ICR comments for OMB 

consideration to OMB by May 18, 2007. 

The Agency will consider and address 

comments received on theinformation 

collection requirements contained in 

this proposal whenit develops the final 

rule. 

C. Regulatory Flexibility Act 

Pursuant to section 605(b) of the 

Regulatory Flexibility Act (RFA), 5 USC 

601 et seq., the Agency hereby certifies 


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that this rule will not have a significant 

adverse economic impact on a 

substantial number of small entities. 

For purposes of assessing the impacts 

of today’s rule on smallentities, small 

entity is defined as: (1) a small business 

according tothe small business size 

standards established by the U.S. Small 

BusinessAdministration (SBA), which 

in this case is a pesticides and 

agriculturalchemical producer (NAICS 

code 325320) with fewer than 

500employees; a crop producer (NAICS 

code 111) with less than $750,000in 

revenues; a college, university, or 

professional school (NAICS 

code611310) with annual revenues less 

than $6.5 million; or an entity 

inresearch and development in the 

physical, engineering, and lifesciences 

(NAICS code 54171) with fewer than 

500 employees; (2) asmall governmental 

jurisdiction that is a government of a 

city, county,town, school district or 

special district with a population of less 

than50,000; and (3) a small organization 

that is any not-for-profit 

enterprisewhich is independently 

owned and operated and is not 

dominant inits field. 

In determining whether a rule has a 

significant economic impacton a 

substantial number of small entities, the 

impact of concern is anysignificant 

adverse economic impact on small 

entities, since the primarypurpose of the 

regulatory flexibility analyses is to 

identify and addressregulatory 

alternatives ‘‘which minimize any 

significant economicimpact of the 

proposed rule on small entities’’ (5 

U.S.C. 603 and 604). Thus, an agency 

may certify that a rule will not have a 

significant economic impact on a 

substantial number of small entities if 

the rule relieves regulatory burden or 

otherwise has a positive economic effect 

on all of the small entities subject to the 

rule. This proposed rule will generate 

savings by exempting PVCP-PIPs with a 

low probability of risk from FIFRA 

requirements. Given the overall 

potential savings attributed to this rule, 

the Agency concludes that this 

proposed action will not result in 

adverse economic impacts, regardless of 

the size of the firm currently developing 

and testing PVCP-PIPs or planning to 

develop and test PVCP-PIPs. Today’s 

action relieves a regulatory burden. 

Nevertheless, the Agency continues to 

be interestedin the potential impacts of 

the proposed rule on small entities 

andwelcomes comments on issues 

related to such impacts. 

D. Unfunded Mandates Reform Act 

Under Title II of the Unfunded 

Mandates Reform Act of 1995 

(UMRA),Public Law 104–4, EPA has 

determined that this action does not 

contain a Federal mandate that may 

result in expenditures of $100 million or 

more forState, local or tribal 

governments, in the aggregate, or on the 

privatesector in any one year. The 

analysis of the cost savings associated 

withthis action are described in Unit V 

of this preamble. The requirementsof 

sections 202, 203, 204 or 205 of UMRA 

which relate to regulatoryrequirements 

that might significantly or uniquely 

affect smallgovernments and to 

regulatory proposals that contain a 

significantFederal intergovernmental 

mandate, respectively, do not apply 

totoday’s rule because the rule affects 

only the private sector, i.e., personsfield 

testing such as universities, 

multinational companies,biotechnology 

companies, chemical companies, seed 

companies;persons selling and 

distributing such as multinational 

companies,biotechnology companies, 

chemical companies, seed companies; 

andpersons using PVCP-PIPs such as 

farmers. 

E. Executive Order 13132 

Pursuant to Executive Order 13132, 

entitled Federalism (64 FR 43255, 

August 10, 1999) EPA has determined 

that this proposed rule does not have 

federalism implications, because it will 

not have substantial direct effects on the 

States, on the relationship between the 

national government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government, as specified in 

Executive Order 13132. The primary 

result of this action is to exempt certain 

PVCP-PIPs from most FIFRA 

requirements. Thus, the requirements of 

section 6 of the Executive Order do not 

apply to this rule. 

F. Executive Order 13175 

Pursuant to Executive Order 13175, 

entitled Consultation and Coordination 

with Indian Tribal Governments (65 FR 

67249, November 9, 2000), EPA has 

concluded that this rule does not have 

tribal implications because it will not 

have any affect on tribal governments, 

on the relationship between the Federal 

government and the Indian tribes, or on 

the distribution of power and 

responsibilities between the Federal 

government and Indian tribes, as 

specified in the Executive Order. EPA is 

proposing to exempt certain PVCP-PIPs 

from most FIFRA requirements. This is 

only expected to affect the private 

sector, not tribes or tribal governments. 

Thus, Executive Order 13175 does not 

apply to this rule. 

G. Executive Order 13211 

This rule is not subject to Executive 

Order 13211, entitled Actions 

Concerning Regulations that 

Significantly Affect Energy Supply, 

Distribution, or Use (66 FR 28355, May 

22, 2001) because it is not designated as 

an ‘‘economically significant’’

regulatory action as defined by 

Executive Order 12866, nor is it likely 

to have any significant adverse effect on 

the supply, distribution, or use of 

energy. 

H. Executive Order 13045 

This rule is not subject to Executive 

Order 13045, entitled Protection of 

Children from Environmental Health 

Risks and Safety Risks (62 FR 19885, 

April 23, 1997), because because it is 

not designated as an ‘‘economically 

significant’’ regulatory action as defined 

in Executive Order 12866 and because 

the Agency does not have reason to 

believe that the environmental health or 

safety risks addressed by this action 

presentdisproportionate risks to 

children. The Agency has determined 

that thePVCP-PIPs that would be 

exempted by this rule pose only a 

lowprobability of risk to human health, 

including the health of infants 

andchildren, and that there is a 

reasonable certainty no harm will 

resultto infants and children from 

aggregate exposure to residues of 

thesePVCP-PIPs in food. Existing 

information suggests there are 

nodisproportionate effects on infants or 

children from dietary or otherexposures. 

EPA’s assessment and the results of its 

assessment arecontained in Unit VIII of 

the companion document 

publishedelsewhere in this issue of the 

Federal Register exempting from the 

FFDCA section 408 requirement of a 

tolerance, residues of the plantvirus coat 

protein portion of a PVCP-PIP. 

I. National Technology Transfer 

Advancement Act 

This rule does not involve a 

regulatory action that would requirethe 

Agency to consider voluntary consensus 

standards pursuant tosection 12(d) of 

the National Technology Transfer and 

AdvancementAct of 1995 (NTTAA), (15 

U.S.C. 272 note). Section 12(d) directs 

EPA to use voluntary consensus 

standards in its regulatory activities 

unless to do so would be inconsistent 

with applicable law or otherwise 

impractical. Voluntaryconsensus 

standards are technical standards (e.g., 

materials specifications, test methods, 

sampling procedures, business 

practices, etc.) that are developed or 

adopted by voluntary consensus 


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standards bodies. The NTTAA requires 

EPA to provide Congress, through OMB, 

explanations when the Agency decides 

not to use available and applicable 

voluntary consensus standards when 

the NTTAA directs the Agency to do so. 

J. Executive Order 12898 

Pursuant to Executive Order 12898, 

entitled Federal Actions to Address 

Environmental Justice in Minority 

Populations and LowIncomePopulations (59 FR 7629, 

February 16, 1994), EPA has 

consideredenvironmental justice related 

issues with regard to the potential 

impactsof this action on the 

environmental and health conditions in 

low incomeand minority communities. 

The Agency is required to considerthe 

potential for differential impacts on 

sensitive sub-populations. 

EPAconsidered available information on 

the sensitivities of subgroups aspertains 

to the exemptions. EPA concluded that 

no subgroup would bedifferentially 

affected. See also the companion 

document ‘‘Exemptionfrom the 

Requirement of a Tolerance under the 

Federal Food, Drug, andCosmetic Act 

for Residues of Plant Virus Coat Proteins 

that are Partof a Plant-Incorporated 

Protectant (PVC-Proteins)’’ published 

elsewherein this issue of the Federal 

Register. 

XI. FIFRA Review Requirements 

In accordance with FIFRA section 

25(d), EPA submitted a draft of 

thisproposed rule to the FIFRA 

Scientific Advisory Panel, the Secretary 

of Agriculture, and to the Committee of 

Agriculture of the House of 

Representatives and the Committee on 

Agriculture, Nutrition, and Forestry of 

the Senate. 

List of Subjects in 40 CFR Part 174 

Environmental protection, 

Administrative practice and procedures, 

Pesticides and pests. 

Dated: April 9, 2007. 

Stephen L. Johnson, 

Administrator. 

Therefore, it is proposed that 40 CFR 

chapter I be amended as follows: 

PART 174—[AMENDED] 

1. The authority citation for part 174 

would continue to read as follows: 

Authority: 7 U.S.C. 136–136y and 21 

U.S.C. 346a and 371. 

2. By alphabetically adding to § 174.3 

new definitions to read as follows: 

§ 174.3 Definitions. 

* * * * * 

Naturally infect means to infect by 

transmission to a plant through direct 

plant-to-plant contact (e.g., pollen or 

seed), an inanimate object (e.g., farm 

machinery), or vector (e.g., arthropod, 

nematode, or fungus). It does not 

include infection by transmission that 

occurs only through intentional human 

intervention, e.g., manual infection in a 

laboratory or greenhouse setting. 

* * * * * 

PVCP-PIP is a plant-incorporated 

protectant derived from one or more 

genes that encode a coat protein of a 

virus that naturally infects plants. This 

includes plant-incorporated protectants 

derived from one or more plant viral 

coat protein genes that produce only 

RNA and no virus-related protein. 

PVC-protein is the plant virus coat 

protein portion of a PVCP-PIP. 

* * * * * 

United States means a State, the 

District of Columbia, the 

Commonwealth of Puerto Rico, the 

Virgin Islands, Guam, the Trust 

Territory of the PacificIslands, and 

American Samoa. 

Unmodified means having or coding 

for an amino acid sequence that is 

identical to an entire coat protein of a 

naturally occurring plant virus. 

* * * * * 

Virtually unmodified means having or 

coding for an amino acid sequence that 

is identical to an entire coat protein of 

a naturally occurring plant virus, except 

for the addition of one or two amino 

acids at the N- and/or C-terminus other 

than cysteine, asparagines, serine, and 

threonine and/or the deletion of one or 

two amino acids at the N- and/or Cterminus. 

Weedy species means a species that is 

an aggressive competitor in natural 

ecosystems. 

* * * * * 

3. In § 174.21 by revising the 

introductory text and paragraph (c) to 

read as follows: 

§ 174.21 General qualifications for 

exemptions. 

A plant-incorporated protectant is 

exempt from the requirements of FIFRA, 

other than the requirements of § 174.71, 

if it meets all of the following criteria. 

Plant-incorporated protectants that are 

not exempt from the requirements of 

FIFRA under this subpart are subject to 

all the requirements of FIFRA. 

* * * * * 

(c) Any inert ingredient that is part of 

the plant-incorporated protectant is on 

the list codified at §§ 174.485 through 

174.486. 

4. By adding § 174.27 to subpart B to 

read as follows: 

§ 174.27 Plant-incorporated protectant 

derived from a coat protein gene(s) from a 

virus(es) that naturally infects plants 

(PVCP-PIP). 

In order for a plant-incorporated 

protectant derived from one or more 

genes that encode a coat protein of a 

virus that naturally infects plants 

(PVCP-PIP) to be exempt, the criteria in 

paragraphs (a), (b), and (c) and the 

requirements in paragraph (d) of this 

section must all be satisfied. 

(a) The criterion in paragraph (a) of 

this section is satisfied if either 

paragraph (a)(1) or paragraph (a)(2) of 

this section applies: 

(1) The plant containing the PIP is one 

of the following: anthurium (Anthurium 

spp.), asparagus (Asparagus officinale), 

avocado (Persea americana), banana 

(Musa acuminata), barley (Hordeum 

vulgare), bean (Phaseolus vulgaris), 

cacao (Theobroma cacao), carnation 

(Dianthus caryophyllus), chickpea 

(Cicer arietinum), citrus (Citrus spp., 

e.g., Citrus aurantifolia, Citrus limon, 

Citrus paradisii, Citrus sinensis), coffee 

(Coffea arabica and Coffea canephora), 

corn (Zea maize), cowpea (Vigna 

unguiculata), cucumber (Cucumis 

sativus), gerbera (Gerbera spp.), 

gladiolus (Gladiolus spp.), lentil (Lens 

culinaris), mango (Mangifera indica), 

orchids (Orchidaceae), papaya (Carica 

papaya), pea (Pisum sativum), peanut 

(Arachis hypogaea), pineapple (Ananas 

comosus), potato (Solanum tuberosum), 

soybean (Glycine max), starfruit 

(Averrhoa carambola), sugarcane 

(Saccharum officinarum), or tulips 

(Tulipa spp.). 

(2) The Agency determines after 

review that the plant containing the PIP 

meets paragraphs (a)(2)(i), (a)(2)(ii), and 

(a)(2)(iii) of this section: 

(i) Has no wild or weedy relatives in 

the United States with which it can 

form viable hybrids in nature. 

(ii) Is not a weedy or invasive species 

outside of agricultural fields in the 

United States. 

(iii) Is unlikely to establish weedy or 

invasive populations outside of 

agricultural fields in the United States 

even if the plant contains a PVCP-PIP. 

(b) The criterion in paragraph (b) of 

this section is satisfied if either 

paragraph (b)(1)(i), paragraph (b)(1)(ii), 

or paragraph (b)(2) of this section 

applies: 

(1)(i) The viral pathotype used to 

create the PVCP-PIP has naturally 

infected plants in the United States and 

naturally infects plants of the same 

species as those containing the PVCPPIP, or 

(ii) The genetic material that encodes 

the pesticidal substance or leads to the 

production of the pesticidal substance is 


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inserted only in an inverted repeat 

orientation or lacking an initiation 

codon for protein synthesis such that no 

PVC-protein is produced in the plant. 

(2) The Agency determines after 

review that viruses that naturally infect 

the plant containing the PVCP-PIP are 

unlikely to acquire the coat protein 

sequence through recombination and 

produce a viable virus with significantly 

different properties than either parent 

virus. 

(c) The criterion in paragraph (c) of 

this section is satisfied if either 

paragraph (c)(1) or paragraph (c)(2) of 

this section applies: 

(1) The genetic material that encodes 

the pesticidal substance or leads to the 

production of the pesticidal substance: 

(i) Is inserted only in an inverted 

repeat orientation or lacking an 

initiation codon for protein synthesis 

such that no PVC-protein is produced in 

the plant, or 

(ii) Encodes only a single virtually 

unmodified viral coat protein. Multiple 

PVC-proteins could each separately 

meet this criterion. Chimeric PVCproteins do not qualify. 

(2) The Agency determines after 

review that the genetic material that 

encodes the pesticidal substance or 

leads to the production of the pesticidal 

substance: 

(i) Encodes a protein that is minimally 

modified from a coat protein from a 

virus that naturally infects plants, or 

(ii) Produces no protein. 

(d)(1) Records to support exemption 

determinations made by the developer 

of a PVCP-PIP under paragraphs (a)(1), 

(b)(1), or (c)(1) of this section; to support 

a submission of information under 

paragraphs (a)(2), (b)(2), or (c)(2) of this 

section; or to support a certification 

made by the developer that a PVCP-PIP 

meets § 174.21(b) and/or § 174.21(c) 

must be maintained by the developer of 

the product for the duration of time that 

the PVCP-PIP is sold or distributed. 

Such records must be made available for 

inspection and copying, or otherwise 

submitted to the Agency for review 

upon request by EPA or its duly 

authorized representative. 

(2) Information adequate to support 

claims for an Agency-determined 

exemption must be submitted for review 

to the Office of Pesticide Programs, 

Attention: PVCP-PIP Exemption. 

(3) A statement notifying the Agency 

and certifying the accuracy of any 

determination made by the developer 

that a PVCP-PIP meets § 174.21(b), 

§ 174.21(c), paragraph (a)(1) of this 

section, paragraph (b)(1) of this section, 

and/or paragraph (c)(1) of this section 

must be signed by the developer and 

submitted to the Office of Pesticide 

Programs, Attention: PVCP-PIP 

Exemption. Any such statement must be 

submitted at the time of a first 

submission, if any, of information under 

paragraph (d)(2) of this section for a 

particular PVCP-PIP. If a PVCP-PIP 

satisfies paragraphs (a)(1), (b)(1), and 

(c)(1)) of this section and §§ 174.21(b) 

and (c), the developer must submit a 

notification to the Agency of that 

determination and certify that the 

PVCP-PIP qualifies for exemption under 

FIFRA, i.e., that the PVCP-PIP meets 

§§ 174.21(a), (b), and (c).This 

certification must contain: 

(i) The name of the crop (including 

genus and species) containing the 

PVCP-PIP. 

(ii) The name of the virus from which 

the coat protein gene was derived. 

(iii) The name of the virus(es) to 

which resistance is conferred. 

(iv) When available, a unique 

identifier. 

5. By revising § 174.480 to read as 

follows: 

§ 174.480 Scope and purpose. 

This subpart lists the inert ingredients 

that may be used in a plant-incorporated 

protectant listed in subpart B of this part 

and whose residues are either exempted 

from the requirement of a tolerance 

under FFDCA or no tolerance would 

otherwise be required. 

6. By adding § 174.486 to read as 

follows: 

§ 174.486 Inert ingredients that may be 

used with PIPs in certain plants. 

The following must be used in a plant 

that satisfies § 174.27(a) in order to be 

exempt from the requirements of FIFRA. 

(a) Beta-D-glucuronidase (GUS) from 

Escherichia coli and the genetic material 

necessary for its production. 

(b) Neomycin phosphotransferase II 

(NPTII) and the genetic material 

necessary for its production. 

(c) Phosphomannose isomerase (PMI) 

and the genetic material necessary for 

its production. 

(d) CP4 enolpyruvylshikimate-3- 

phosphate (CP4 EPSPS) and the genetic 

material necessary for its production. 

(e) Glyphosate oxidoreductase (GOX 

or GOXv247) and the genetic material 

necessary for its production. 

(f) Phosphinothricin acetyltransferase 

(PAT) and the genetic material 

necessary for its production. 

(g) Partial tetracycline resistance gene 

under the control of a bacterial promoter 

as present in papaya line 55–1. 

[FR Doc. E7–7297 Filed 4–17–07; 8:45 am] 

BILLING CODE 6560–50–S 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 174 

[EPA–HQ–OPP–2006–0643; FRL–8100–5] 

RIN 2070–AD49 

Exemption from the Requirement of a 

Tolerance under the Federal Food, 

Drug, and Cosmetic Act for Residues 

of Plant Virus Coat Proteins that are 

Part of a Plant-Incorporated Protectant 

(PVC-Proteins); Supplemental 

Proposal 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: EPA is proposing to exempt 

from the Federal Food, Drug, and 

Cosmetic Act (FFDCA) section 408 

requirement of a tolerance, residues of 

coat proteins from viruses that naturally 

infect plants that humans consume 

when such coat proteins are produced 

in living plants as part of a plantincorporated protectant (PIP) and the 

criteria proposed for this exemption are 

met. EPA believes there is a reasonable 

certainty that no harm will result from 

aggregate exposure to such residues, 

including all anticipated dietary 

exposures and all other exposures for 

which there is reliable information. This 

proposed exemption would eliminate 

the need to establish a maximum 

permissible level in food for these 

residues. 

DATES: Comments must be received on 

or before July 17, 2007. 

ADDRESSES: Submit your comments, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2006–0643, by 

one of the following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. Deliveries 

are only accepted during the Docket’s 

normal hours of operation (8:30 a.m. to 

4 p.m., Monday through Friday, 

excluding legal holidays). Special 

arrangements should be made for 

deliveries of boxed information. The 

Docket Facility telephone number is 

(703) 305–5805. 

• Instructions: Direct your comments 

to docket ID number EPA–HQ–OPP–


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